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Joo SG, Kim JM, Lee HL, Go MJ, Kim TY, Kim JH, Lee HS, Eo HJ, Kim HJ, Heo HJ. Synurus deltoides Alleviates Anti-Depressive Like Behavior Dysfunction Induced by Chronic Unpredictable Mild Stress via Stress-Related CRF/TLR Pathway. J Microbiol Biotechnol 2025; 35:e2501043. [PMID: 40374544 PMCID: PMC12099629 DOI: 10.4014/jmb.2501.01043] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/27/2025] [Revised: 03/26/2025] [Accepted: 03/26/2025] [Indexed: 05/17/2025]
Abstract
This study was aimed at assessing the protective effect of the 80% ethanolic extract of Synurus deltoides (EESD) on chronic unpredictable mild stress (CUMS)-induced depressive-like behavior dysfunction. The bioactive compounds of S. deltoides were identified as quinic acid, chlorogenic acid, rutin, 1,3-dicaffeoylquinic acid, and dicaffeoylsuccinoylquinic acid. EESD and bioactive compounds in EESD significantly protected corticosterone-induced hippocampal cellular death and reactive oxygen species (ROS) contents compared to vitamin C in HT22 cells. By conducting the sucrose preference test, forced swimming test, open field test, and tail suspension test, EESD was found to significantly suppress depression-like behavior. EESD effectively reduced mitochondrial dysfunction by regulating cerebral ROS levels, mitochondrial membrane potential, and ATP contents. EESD showed a considerable regulatory effect by regulating serum stress hormones including corticosterone, norepinephrine, serotonin, 5-hydroxyindoleacetic acid, and melatonin. In addition, EESD significantly suppressed stress-related CRF pathway, inflammatory TLR pathway, and apoptotic signal in cerebral tissues. These results suggest that EESD might be a natural plant substance that improves CUMS-induced behavior abnormality by regulating inflammation and hormonal changes in brain tissue. In the future, additional clinical trials or efficacy evaluations of individual compounds of EESD will be needed to confirm the bioactivity ability and usability of EESD.
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Affiliation(s)
- Seung Gyum Joo
- Division of Applied Life Science (BK21), Institute of Agriculture and Life Science, Gyeonsang National University, Jinju 52828, Republic of Korea
| | - Jong Min Kim
- Division of Applied Life Science (BK21), Institute of Agriculture and Life Science, Gyeonsang National University, Jinju 52828, Republic of Korea
- Korea Food Research Institute, Wanju-gun 55365, Republic of Korea
| | - Hyo Lim Lee
- Division of Applied Life Science (BK21), Institute of Agriculture and Life Science, Gyeonsang National University, Jinju 52828, Republic of Korea
| | - Min Ji Go
- Division of Applied Life Science (BK21), Institute of Agriculture and Life Science, Gyeonsang National University, Jinju 52828, Republic of Korea
| | - Tae Yoon Kim
- Division of Applied Life Science (BK21), Institute of Agriculture and Life Science, Gyeonsang National University, Jinju 52828, Republic of Korea
| | - Ju Hui Kim
- Division of Applied Life Science (BK21), Institute of Agriculture and Life Science, Gyeonsang National University, Jinju 52828, Republic of Korea
| | - Han Su Lee
- Division of Applied Life Science (BK21), Institute of Agriculture and Life Science, Gyeonsang National University, Jinju 52828, Republic of Korea
| | - Hyun Ji Eo
- Division of Special Forest Resources, Department of Forest Bio-resources, National Instiute of Forest Science, Seoul 0245, Republic of Korea
| | - Hyun-Jin Kim
- Division of Applied Life Science (BK21), Institute of Agriculture and Life Science, Gyeonsang National University, Jinju 52828, Republic of Korea
| | - Ho Jin Heo
- Division of Applied Life Science (BK21), Institute of Agriculture and Life Science, Gyeonsang National University, Jinju 52828, Republic of Korea
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Zhang X, Wang H, Kilpatrick LA, Dong TS, Gee GC, Beltran-Sanchez H, Wang MC, Vaughan A, Church A. Connectome modeling of discrimination exposure: Impact on your social brain and psychological symptoms. Prog Neuropsychopharmacol Biol Psychiatry 2025; 139:111366. [PMID: 40239889 DOI: 10.1016/j.pnpbp.2025.111366] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/21/2024] [Revised: 03/22/2025] [Accepted: 04/12/2025] [Indexed: 04/18/2025]
Abstract
Discrimination is a social stressor that is associated with adverse health outcomes, but the underlying neural mechanisms remain unclear. The fusiform, including the fusiform face area (FFA) plays a critical role in face perception especially regarding hostile faces during discrimination exposure; and are key regions involved in social cognition. We compared resting-state spontaneous activity and connectivity of the fusiform and FFA, between 153 individuals (110 women) with high (N = 73) and low (N = 80) levels of discrimination (measured by the Everyday Discrimination Scale) and evaluated the relationships of these brain signatures with psychological outcomes and stress-related neurotransmitters. Discrimination-related group differences showed altered fusiform signal fluctuation dynamics (Hurst exponent) and connectivity. These alterations predicted discrimination experiences and correlated with anxiety, depression, and cognitive difficulties. A molecular architecture analysis using cross-modal spatial correlation of brain signatures and nuclear imaging derived estimates of stress-related neurotransmitters demonstrated overlap between discrimination-related connectivity and dopamine, serotonin, gamma-aminobutyric acid (GABA), and acetylcholine. Discrimination exposure associated with alterations in the fusiform and face processing area may reflect enhanced baseline preparedness and vigilance towards facial stimuli and decreased top-down regulation of potential threats. These brain alterations may contribute to increased vulnerability for the development of mental health symptoms, demonstrating clinical relevance of social cognition in stressful interpersonal relationships.
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Affiliation(s)
- Xiaobei Zhang
- G. Oppenheimer Center for Neurobiology of Stress & Resilience, at UCLA, United States of America; Vatche and Tamar Manoukian Division of Digestive Diseases, at UCLA, United States of America; David Geffen School of Medicine at UCLA, United States of America; University of California, Los Angeles, United States of America; UCLA Goodman-Luskin Microbiome Center, United States of America
| | - Hao Wang
- G. Oppenheimer Center for Neurobiology of Stress & Resilience, at UCLA, United States of America; State Key Laboratory of Digital Medical Engineering, Key Laboratory of Biomedical Engineering of Hainan Province, School of Biomedical Engineering, Hainan University, China
| | - Lisa A Kilpatrick
- G. Oppenheimer Center for Neurobiology of Stress & Resilience, at UCLA, United States of America; Vatche and Tamar Manoukian Division of Digestive Diseases, at UCLA, United States of America; David Geffen School of Medicine at UCLA, United States of America; University of California, Los Angeles, United States of America; UCLA Goodman-Luskin Microbiome Center, United States of America
| | - Tien S Dong
- G. Oppenheimer Center for Neurobiology of Stress & Resilience, at UCLA, United States of America; Vatche and Tamar Manoukian Division of Digestive Diseases, at UCLA, United States of America; David Geffen School of Medicine at UCLA, United States of America; University of California, Los Angeles, United States of America; UCLA Goodman-Luskin Microbiome Center, United States of America
| | - Gilbert C Gee
- Department of Community Health Sciences Fielding School of Public Health, United States of America; California Center for Population Research, UCLA, United States of America
| | - Hiram Beltran-Sanchez
- Department of Community Health Sciences Fielding School of Public Health, United States of America; California Center for Population Research, UCLA, United States of America
| | - May C Wang
- Department of Community Health Sciences Fielding School of Public Health, United States of America
| | - Allison Vaughan
- G. Oppenheimer Center for Neurobiology of Stress & Resilience, at UCLA, United States of America; Vatche and Tamar Manoukian Division of Digestive Diseases, at UCLA, United States of America; David Geffen School of Medicine at UCLA, United States of America; University of California, Los Angeles, United States of America; UCLA Goodman-Luskin Microbiome Center, United States of America
| | - Arpana Church
- G. Oppenheimer Center for Neurobiology of Stress & Resilience, at UCLA, United States of America; Vatche and Tamar Manoukian Division of Digestive Diseases, at UCLA, United States of America; David Geffen School of Medicine at UCLA, United States of America; University of California, Los Angeles, United States of America; UCLA Goodman-Luskin Microbiome Center, United States of America.
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Dobolyi A. Integrating the COM-B model into behavioral neuroscience: A framework for understanding animal behavior. Prog Neuropsychopharmacol Biol Psychiatry 2025; 138:111346. [PMID: 40154911 DOI: 10.1016/j.pnpbp.2025.111346] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/14/2024] [Revised: 03/24/2025] [Accepted: 03/24/2025] [Indexed: 04/01/2025]
Abstract
In light of the intricate nature of animal behavior regulation, a theoretical model is proposed, grounded in the COM-B (Capability, Opportunity, Motivation - Behavior) framework, which has gained considerable traction in the domain of human behavioral intervention. When extending the COM-B model to behavioral neuroscience, we first discuss the utility of the model in animal research, particularly its capacity to integrate environmental and social factors, and enhance cross-species comparisons, including animal-to-human translations and evolutionary considerations. The subsequent discussion then summarizes the advantages of utilizing the COM-B model in neuroscience are summarized, including the facilitation of a systems-level understanding of behavior and the establishment of a link between neural mechanisms and specific behavioral components. The experimental design for the application of the COM-B model in neuroscience is proposed to elucidate the brain regulatory processes that govern behavior. Finally, three specific examples are provided to illustrate the theoretical considerations, namely feeding and social behavior, and the role of neuromodulators in the control of behavior.
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Affiliation(s)
- Arpád Dobolyi
- Laboratory of Neuromorphology, Department of Anatomy, Histology and Embryology, Semmelweis University, Budapest, Hungary; Laboratory of Molecular and Systems Neurobiology, Department of Physiology and Neurobiology, Eötvös Loránd University, Budapest, Hungary.
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Ismaylova E, Nemoda Z, Booij L. Brain serotonin, oxytocin, and their interaction: Relevance for eating disorders. J Psychopharmacol 2025; 39:187-200. [PMID: 39745000 PMCID: PMC11843796 DOI: 10.1177/02698811241309617] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/22/2025]
Abstract
INTRODUCTION Eating disorders are characterized by maladaptive eating behaviors and preoccupations around body shape, weight, and eating. The serotonin system has been among the most widely studied neurobiological factors in relation to eating disorders. Recent research also highlighted the role of oxytocin. AIMS AND METHODS This article aims to review animal and human studies on the involvement of central serotonin and oxytocin, and their interplay in eating disorders in particular. We synthesize results from studies using animal models of eating disorders and from research conducted in healthy individuals and clinical populations. RESULTS/OUTCOMES Altered serotonin neurotransmission and oxytocin levels in the brain-particularly in the hypothalamus, brainstem, and limbic regions-were associated with disturbances in eating behaviors and related maladaptive cognitions and emotions. These brain regions were found to constitute a typical neural network through which both central serotonin and oxytocin might operate in a bidirectional manner. CONCLUSIONS/INTERPRETATION Based on the preceding findings, we describe a developmental biopsychosocial model relevant to eating disorders, including the role of serotonin-oxytocin interactions in the brain. While it is clear that eating disorders are multifactorial in which many biopsychosocial pathways are involved, the current review highlights the importance of well-designed translational research when studying mechanisms of serotonin-oxytocin interactions in the brain. Such research would help to better understand the effects of joint central oxytocin and serotonin administration as a possible preventive or therapeutic intervention for eating disorders.
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Affiliation(s)
- Elmira Ismaylova
- Eating Disorders Continuum and Research Center, Douglas Mental Health University Institute, Montreal, QC, Canada
- Department of Psychology, Concordia University, Montreal, QC, Canada
| | - Zsofia Nemoda
- Eating Disorders Continuum and Research Center, Douglas Mental Health University Institute, Montreal, QC, Canada
- Department of Molecular Biology, Semmelweis University, Budapest, Hungary
| | - Linda Booij
- Eating Disorders Continuum and Research Center, Douglas Mental Health University Institute, Montreal, QC, Canada
- Department of Psychology, Concordia University, Montreal, QC, Canada
- Department of Psychiatry, McGill University, Montreal, QC, Canada
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Golonka K, Gulla B, Kościelniak D, Darczuk D, Cienkosz-Stepanczak B, Bystrowska B, Fortuna D, Kozicz T, Krzyściak W. Sensory processing sensitivity in adult dental patients and its relation to perceived stress, cortisol, and serotonin secretion. Sci Rep 2025; 15:7328. [PMID: 40025052 PMCID: PMC11873274 DOI: 10.1038/s41598-025-90263-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/31/2024] [Accepted: 02/11/2025] [Indexed: 03/04/2025] Open
Abstract
Sensory processing sensitivity (SPS) is a biologically determined trait that influences how individuals respond to external and internal stimuli. A high level of SPS is characterized by three factors: increased emotional reactivity, heightened sensitivity to subtle stimuli, and greater susceptibility to overstimulation, all of which may impact well-being and health. This study examined the relationships between SPS, perceived stress, affect, and biochemical responses in adult dental patients (N = 157) on the day of a routine dental visit. Biochemical measures included morning cortisol and serotonin secretion (saliva samples), and cortisol concentration accumulated in recent months (hair sample). Perceived stress and negative and positive affect were assessed while patients waited for a dental procedure. The correlation analysis revealed that higher SPS level was associated with elevated hair cortisol and more negative affect. Cluster analyses tested SPS and its factors independently, revealing that individuals with higher SPS had higher cortisol levels in saliva and hair samples, as well as greater perceived stress and negative affect. Salivary serotonin levels showed varied relationships with different SPS factors, indicating the need to analyze SPS as a multidimensional construct. The results indicate that increased hair and salivary cortisol may be considered as biomarkers of SPS. In the context of patient-centered care, considering SPS levels may contribute to enhanced motivation for regular dental visits and improved treatment adherence.
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Affiliation(s)
- Krystyna Golonka
- Institute of Applied Psychology, Faculty of Management and Social Communication, Jagiellonian University, 30-348, Kraków, Poland.
| | - Bożena Gulla
- Institute of Applied Psychology, Faculty of Management and Social Communication, Jagiellonian University, 30-348, Kraków, Poland
| | - Dorota Kościelniak
- Department of Developmental Dentistry, Institute of Dentistry, Jagiellonian University Medical College, 31-155, Kraków, Poland
| | - Dagmara Darczuk
- Department of Periodontology, Prophylaxis and Oral Medicine, Institute of Dentistry, Jagiellonian University Medical College, 31-155, Kraków, Poland
| | - Beata Cienkosz-Stepanczak
- Laboratory of Anthropology, Institute of Zoology and Biomedical Research, Faculty of Biology, Jagiellonian University, Kraków, 30-387, Poland
| | - Beata Bystrowska
- Department of Toxicology, Faculty of Pharmacy, Jagiellonian University Medical College, 30-688, Kraków, Poland
| | - Dominika Fortuna
- Doctoral School in the Social Sciences, Jagiellonian University, 31-010, Kraków, Poland
| | - Tamas Kozicz
- Department of Genetics and Genomic Sciences, Icahn School of Medicine, Mount Sinai, New York, NY, 10029, USA
| | - Wirginia Krzyściak
- Department of Medical Diagnostics, Faculty of Pharmacy, Jagiellonian University Medical College, 30-688, Kraków, Poland
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Muroi Y, Ishii T. Neuronal stress-coping mechanisms in postpartum females. Neurosci Res 2025:S0168-0102(25)00032-X. [PMID: 39978735 DOI: 10.1016/j.neures.2025.02.006] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/25/2024] [Revised: 02/05/2025] [Accepted: 02/12/2025] [Indexed: 02/22/2025]
Abstract
Animals exhibit a wide range of stress responses aimed at restoring homeostasis and promoting adaptation. In response to stress, they employ coping mechanisms to maintain physiological balance. Dysregulated stress-coping strategies have been associated with mental disorders, including depression, anxiety, and post-traumatic stress disorder. Understanding the neuronal mechanisms that regulate stress-coping is critical for elucidating normal physiological responses and addressing the pathological processes underlying these disorders. Stress responses are influenced by sex and life stage, with notable variability in the prevalence and severity of mental disorders based on these factors. Stress-coping mechanisms are pivotal in determining the vulnerability or resilience of an individual to stress. Thus, identifying differences in stress-coping strategies between sexes and across life stages is essential for advancing prevention and treatment strategies for stress-related mental disorders. This review explores the neuronal mechanisms underlying stress responses, emphasizing the distinct stress-coping strategies utilized by postpartum females. Highlighting these differences underscores the need for targeted prevention and treatment approaches that consider sex- and life stage-specific variations in stress-coping mechanisms.
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Affiliation(s)
- Yoshikage Muroi
- Department of Veterinary Medicine, Obihiro University of Agriculture and Veterinary Medicine, National University Cooperation Hokkaido Higher Education and Research, Hokkaido 080-8555, Japan.
| | - Toshiaki Ishii
- Department of Veterinary Medicine, Obihiro University of Agriculture and Veterinary Medicine, National University Cooperation Hokkaido Higher Education and Research, Hokkaido 080-8555, Japan
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Abbasi-Maleki S, Nakhaei B, Mehr SR, Moradikor N. Introduction to neurobiology and pharmacology of stress. PROGRESS IN BRAIN RESEARCH 2025; 291:1-19. [PMID: 40222775 DOI: 10.1016/bs.pbr.2025.01.006] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 04/15/2025]
Abstract
In order to improve individual and community health outcomes, stress research is crucial for developing our understanding of human biology, psychology, and social dynamics. It also informs therapeutic practices, public health campaigns, and educational activities. The chapter explores how neurotransmitters, including glutamate, GABA, adrenaline, norepinephrine, serotonin, dopamine, and adrenaline, mediate stress responses, impact mood and behavior, and play a part in a number of stress-related disorders. The relevance of focused research and therapy approaches aimed at reestablishing equilibrium within these systems is highlighted by the fact that dysregulation of these neurotransmitters can exacerbate health problems. Additionally, it is investigated how the amygdala, hippocampus, and prefrontal cortex interact to process emotions, build resilience, and determine an individual's susceptibility to stress. These interactions are regulated by both neuroplasticity and hereditary and epigenetic factors. The chapter discusses the pharmaceutical approach to stress management, which includes a variety of drugs such as beta-blockers, anxiolytics, and antidepressants that work by targeting different neurotransmitter systems to reduce anxiety and mood disorders. Even while these therapies work, they may have negative consequences and side effects that should be carefully considered in clinical settings. The chapter promotes a comprehensive approach to stress management that combines medication, lifestyle changes, psychotherapy, and stress-reduction methods. Healthcare workers can improve patient care and ultimately the health and quality of life for people with stress-related disorders by knowing the complexity of pharmaceutical therapies and how they affect the stress response.
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Affiliation(s)
- Saeid Abbasi-Maleki
- Pharmaceutical Sciences Research Center, Health Institute, Kermanshah University of Medical Sciences, Kermanshah, Iran
| | - Babak Nakhaei
- Department of Pathobiology, Faculty of Veterinary Medicine, Urmia Branch, Islamic Azad University, Urmia, Iran
| | - Samira Rostami Mehr
- Pharmaceutical Sciences Research Center, Health Institute, Kermanshah University of Medical Sciences, Kermanshah, Iran
| | - Nasrollah Moradikor
- International Center for Neuroscience Research, Institute for Intelligent Research, Tbilisi, Georgia.
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Gryksa K, Schäfer T, Gareis F, Fuchs E, Royer M, Schmidtner AK, Bludau A, Neumann ID. Beyond fur color: differences in socio-emotional behavior and the oxytocin system between male BL6 and CD1 mice in adolescence and adulthood. Front Neurosci 2024; 18:1493619. [PMID: 39717700 PMCID: PMC11663876 DOI: 10.3389/fnins.2024.1493619] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/09/2024] [Accepted: 11/08/2024] [Indexed: 12/25/2024] Open
Abstract
Introduction The development of stress-related psychopathologies, often associated with socio-emotional dysfunctions, is crucially determined by genetic and environmental factors, which shape the individual vulnerability or resilience to stress. Especially early adolescence is considered a vulnerable time for the development of psychopathologies. Various mouse strains are known to age-dependently differ in social, emotional, and endocrine stress responses based on genetic and epigenetic differences. This highlights the importance of the qualified selection of an adequate strain and age for any biomedical research. Neuropeptides like oxytocin (OXT) can contribute to individual and strain-dependent differences in emotional and social behaviors. Methods In this study, we compared anxiety- and fear-related, as well as social behavior and pain perception between male adolescent and adult mice of two commonly used strains, C57BL/6N (BL6) and CD1. Results We revealed BL6 mice as being more anxious, less social, and more susceptible toward non-social and social trauma, both in adolescence and adulthood. Furthermore, during development from adolescence toward adulthood, BL6 mice lack the reduction in fear- and anxiety-related behavior seen in adult CD1 mice and show even higher social fear-responses and perception of noxious stimuli during adulthood. Analysis of the OXT system, by means of receptor autoradiography and immunohistochemistry, showed strain- and age-specific differences in OXT receptor (OXTR) binding in relevant brain regions, but no differences in the number of hypothalamic OXT neurons. However, intracerebroventricular infusion of OXT did neither reduce the high level of anxiety-related nor of social fear-related behavior in adult BL6 mice. Discussion In summary, we show that male BL6 mice present an anxious and stress vulnerable phenotype in adolescence, which further exacerbates in adulthood, whereas CD1 mice show a more resilient socio-emotional state both in adolescence as well as during adulthood. These consistent behavioral differences between the two strains might only be partly mediated by differences in the OXT system but highlight the influence of early-life environment on socio-emotional behavior.
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Elfakharany SA, Eskaros SS, Azhary NME, Abdelmonsif DA, Zeitoun TM, Ammar GAG, Hatem YA. Neuroprotective Role of Selenium Nanoparticles Against Behavioral, Neurobiochemical and Histological Alterations in Rats Subjected to Chronic Restraint Stress. Mol Neurobiol 2024; 61:10159-10181. [PMID: 38703343 PMCID: PMC11584447 DOI: 10.1007/s12035-024-04196-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/28/2024] [Accepted: 04/22/2024] [Indexed: 05/06/2024]
Abstract
Chronic stress induces changes in the prefrontal cortex and hippocampus. Selenium nanoparticles (SeNPs) showed promising results in several neurological animal models. The implementation of SeNPs in chronic restraint stress (CRS) remains to be elucidated. This study was done to determine the possible protective effects of selenium nanoparticles on behavioral changes and brain oxidative stress markers in a rat model of CRS. 50 rats were divided into three groups; control group (n = 10), untreated CRS group (n = 10) and CRS-SeNPs treated group (n = 30). Restraint stress was performed 6 h./day for 21 days. Rats of CRS-SeNPs treated group received 1, 2.5 or 5 mg/kg SeNPs (10 rats each) by oral gavage for 21 days. Rats were subjected to behavioral assessments and then sacrificed for biochemical and histological analysis of the prefrontal cortex and hippocampus. Prefrontal cortical and hippocampal serotonin levels, oxidative stress markers including malondialdehyde (MDA), reduced glutathione (GSH) and glutathione peroxidase (GPx), tumor necrosis factor alpha (TNF-α) and caspase-3 were assessed. Accordingly, different doses of SeNPs showed variable effectiveness in ameliorating disease parameters, with 2.5 mg/kg dose of SeNPs showing the best improving results in all studied parameters. The present study exhibited the neuroprotective role of SeNPs in rats subjected to CRS and proposed their antioxidant, anti-inflammatory and anti-apoptotic effects as the possible mechanism for increased prefrontal cortical and hippocampal serotonin level, ameliorated anxiety-like and depressive-like behaviors and improved prefrontal cortical and hippocampal histological architecture.
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Affiliation(s)
- Sarah A Elfakharany
- Department of Medical Physiology, Faculty of Medicine, University of Alexandria, Al-Mouassat Medical Campus, El Hadara, Alexandria, Egypt.
| | - Samir S Eskaros
- Department of Medical Physiology, Faculty of Medicine, University of Alexandria, Al-Mouassat Medical Campus, El Hadara, Alexandria, Egypt
| | - Nesrine M El Azhary
- Department of Medical Physiology, Faculty of Medicine, University of Alexandria, Al-Mouassat Medical Campus, El Hadara, Alexandria, Egypt
| | - Doaa A Abdelmonsif
- Department of Medical Biochemistry, Faculty of Medicine, University of Alexandria, Al- Moussat Medical Campus, El Hadara, Alexandria, Egypt
| | - Teshreen M Zeitoun
- Department of Histology and Cell Biology, Faculty of Medicine, University of Alexandria, Al-Moussat Medical Campus, El Hadara, Alexandria, Egypt
| | - Gamal A G Ammar
- Biotechnology Unit, Plant Production Department (PPD), Arid Lands Cultivation Research Institute (ALCRI), City of Scientific Research and Technological Applications (SRTA-City), New Borg El‑Arab City, Alexandria, Egypt
| | - Youssef A Hatem
- Department of Medical Physiology, Faculty of Medicine, University of Alexandria, Al-Mouassat Medical Campus, El Hadara, Alexandria, Egypt
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Lukow PB, Lowther M, Pike AC, Yamamori Y, Chavanne AV, Gormley S, Aylward J, McCloud T, Goble T, Rodriguez-Sanchez J, Tuominen EW, Buehler SK, Kirk P, Robinson OJ. Amygdala activity after subchronic escitalopram administration in healthy volunteers: A pharmaco-functional magnetic resonance imaging study. J Psychopharmacol 2024; 38:1071-1082. [PMID: 39364684 PMCID: PMC11531087 DOI: 10.1177/02698811241286773] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 10/05/2024]
Abstract
BACKGROUND Selective serotonin reuptake inhibitors (SSRIs) are used for the treatment of several conditions including anxiety disorders, but the basic neurobiology of serotonin function remains unclear. The amygdala and prefrontal cortex are strongly innervated by serotonergic projections and have been suggested to play an important role in anxiety expression. However, serotonergic function in behaviour and SSRI-mediated neurobiological changes remain incompletely understood. AIMS To investigate the neural correlates of subchronic antidepressant administration. METHODS We investigated whether the 2- to 3-week administration of a highly selective SSRI (escitalopram) would alter brain activation on a task robustly shown to recruit the bilateral amygdala and frontal cortices in a large healthy volunteer sample. Participants performed the task during a functional magnetic resonance imaging acquisition before (n = 96) and after subchronic escitalopram (n = 46, days of administration mean (SD) = 15.7 (2.70)) or placebo (n = 40 days of administration mean (SD) = 16.2 (2.90)) self-administration. RESULTS Compared to placebo, we found an elevation in right amygdala activation to the task after escitalopram administration without significant changes in mood. This effect was not seen in the left amygdala, the dorsomedial region of interest, the subgenual anterior cingulate cortex or the right fusiform area. There were no significant changes in connectivity between the dorsomedial cortex and amygdala or the subgenual anterior cingulate cortex after escitalopram administration. CONCLUSIONS To date, this most highly powered study of subchronic SSRI administration indicates that, contrary to effects often seen in patients with anxiety disorders, subchronic SSRI treatment may increase amygdala activation in healthy controls. This finding highlights important gaps in our understanding of the functional role of serotonin.
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Affiliation(s)
- Paulina B Lukow
- Institute of Cognitive Neuroscience, University College London, London, UK
| | - Millie Lowther
- Institute of Cognitive Neuroscience, University College London, London, UK
| | - Alexandra C Pike
- Institute of Cognitive Neuroscience, University College London, London, UK
- Department of Psychology & York Biomedical Research Institute, University of York, York, UK
| | - Yumeya Yamamori
- Institute of Cognitive Neuroscience, University College London, London, UK
| | - Alice V Chavanne
- Institute of Cognitive Neuroscience, University College London, London, UK
- Université Paris-Saclay, Institut National de la Santé et de la Recherche Médicale, INSERM U1299 “Trajectoires Développementales Psychiatrie,” Ecole Normale Supérieure Paris-Saclay, CNRS UMR 9010, Centre Borelli, Gif-sur-Yvette, France
- Department of Psychology, Humboldt-Universität zu Berlin, Berlin, Germany
| | - Siobhan Gormley
- Institute of Cognitive Neuroscience, University College London, London, UK
| | - Jessica Aylward
- Institute of Cognitive Neuroscience, University College London, London, UK
| | - Tayla McCloud
- Institute of Cognitive Neuroscience, University College London, London, UK
- UCL Division of Psychiatry, Maple House, London, UK
| | - Talya Goble
- Institute of Cognitive Neuroscience, University College London, London, UK
| | - Julia Rodriguez-Sanchez
- Institute of Cognitive Neuroscience, University College London, London, UK
- Centre for Medical Image Computing, Department of Computer Science, University College London, London, UK
| | - Ella W Tuominen
- Institute of Cognitive Neuroscience, University College London, London, UK
| | - Sarah K Buehler
- Institute of Cognitive Neuroscience, University College London, London, UK
| | - Peter Kirk
- Institute of Cognitive Neuroscience, University College London, London, UK
- Emotion and Development Branch, National Institute of Mental Health, Bethesda, MD, USA
| | - Oliver J Robinson
- Institute of Cognitive Neuroscience, University College London, London, UK
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11
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Pietsch C, Pawlak P, Konrad J. Acute Stress Effects over Time on the Gene Expression and Neurotransmitter Patterns in the Carp ( Cyprinus carpio) Brain. Animals (Basel) 2024; 14:3413. [PMID: 39682377 DOI: 10.3390/ani14233413] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/31/2024] [Revised: 11/21/2024] [Accepted: 11/22/2024] [Indexed: 12/18/2024] Open
Abstract
Changes in gene expression in carps' brains over time following acute stressors has not been studied in detail so far. Consequently, a stress trial with juvenile common carp was conducted to investigate transcriptomic differences in four brain parts in response to acute negative stressors and feed reward, focusing on appetite-related genes, serotonergic and dopaminergic pathways, and other involved systems, at 30, 60, and 90 min after treatments. The treatments showed pronounced effects on the gene expression patterns across brain parts compared to control fish. Notably, npy expression increased in the telencephalon following negative stressors and feed reward, suggesting a stress-coping mechanism by promoting food intake. Unlike zebrafish, cart expression in carp showed varying responses, indicating species-specific regulation of appetite and stress. Serotonergic and dopaminergic pathways were also affected, with alterations in the respective receptors' expression, confirming their roles in stress and reward processing. Additionally, this study highlights the involvement of the opioid- and gamma-aminobutyric acid systems in stress and feeding regulation across brain parts. Furthermore, principal component analyses revealed that neurotransmitter levels in the different brain parts contribute to the explained variance. These findings deepen our understanding of how different fish species react to acute stress and rewards.
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Affiliation(s)
- Constanze Pietsch
- School of Agricultural, Forest and Food Sciences (HAFL), Bern University of Applied Sciences (BFH), 3052 Zollikofen, Switzerland
| | - Paulina Pawlak
- School of Agricultural, Forest and Food Sciences (HAFL), Bern University of Applied Sciences (BFH), 3052 Zollikofen, Switzerland
| | - Jonathan Konrad
- School of Agricultural, Forest and Food Sciences (HAFL), Bern University of Applied Sciences (BFH), 3052 Zollikofen, Switzerland
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12
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Ferraz-Bannitz R, Ozturk B, Cummings C, Efthymiou V, Casanova Querol P, Poulos L, Wang H, Navarrete V, Saeed H, Mulla CM, Pan H, Dreyfuss JM, Simonson DC, Sandoval DA, Patti ME. Postprandial metabolomics analysis reveals disordered serotonin metabolism in post-bariatric hypoglycemia. J Clin Invest 2024; 134:e180157. [PMID: 39264731 PMCID: PMC11527454 DOI: 10.1172/jci180157] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/21/2024] [Accepted: 09/06/2024] [Indexed: 09/14/2024] Open
Abstract
BACKGROUNDBariatric surgery is a potent therapeutic approach for obesity and type 2 diabetes but can be complicated by post-bariatric hypoglycemia (PBH). PBH typically occurs 1-3 hours after meals, in association with exaggerated postprandial levels of incretins and insulin.METHODSTo identify mediators of disordered metabolism in PBH, we analyzed the plasma metabolome in the fasting state and 30 and 120 minutes after mixed meal in 3 groups: PBH (n = 13), asymptomatic post-Roux-en-Y gastric bypass (post-RYGB) (n = 10), and nonsurgical controls (n = 8).RESULTSIn the fasting state, multiple tricarboxylic acid cycle intermediates and the ketone β-hydroxybutyrate were increased by 30%-80% in PBH versus asymptomatic. Conversely, multiple amino acids (branched-chain amino acids, tryptophan) and polyunsaturated lipids were reduced by 20%-50% in PBH versus asymptomatic. Tryptophan-related metabolites, including kynurenate, xanthurenate, and serotonin, were reduced 2- to 10-fold in PBH in the fasting state. Postprandially, plasma serotonin was uniquely increased 1.9-fold in PBH versus asymptomatic post-RYGB. In mice, serotonin administration lowered glucose and increased plasma insulin and GLP-1. Moreover, serotonin-induced hypoglycemia in mice was blocked by the nonspecific serotonin receptor antagonist cyproheptadine and the specific serotonin receptor 2 antagonist ketanserin.CONCLUSIONTogether these data suggest that increased postprandial serotonin may contribute to the pathophysiology of PBH and provide a potential therapeutic target.FUNDINGNational Institutes of Health (NIH) grant R01-DK121995, NIH grant P30-DK036836 (Diabetes Research Center grant, Joslin Diabetes Center), and Fundação de Amparo à Pesquisa do Estado de São Paulo grant 2018/22111-2.
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Affiliation(s)
- Rafael Ferraz-Bannitz
- Research Division, Joslin Diabetes Center, Boston, Massachusetts, USA
- Harvard Medical School, Boston, Massachusetts, USA
| | - Berkcan Ozturk
- Research Division, Joslin Diabetes Center, Boston, Massachusetts, USA
- Harvard Medical School, Boston, Massachusetts, USA
| | - Cameron Cummings
- Research Division, Joslin Diabetes Center, Boston, Massachusetts, USA
| | - Vissarion Efthymiou
- Research Division, Joslin Diabetes Center, Boston, Massachusetts, USA
- Harvard Medical School, Boston, Massachusetts, USA
| | - Pilar Casanova Querol
- Research Division, Joslin Diabetes Center, Boston, Massachusetts, USA
- Harvard Medical School, Boston, Massachusetts, USA
| | - Lindsay Poulos
- Research Division, Joslin Diabetes Center, Boston, Massachusetts, USA
- Harvard Medical School, Boston, Massachusetts, USA
| | - Hanna Wang
- Research Division, Joslin Diabetes Center, Boston, Massachusetts, USA
| | - Valerie Navarrete
- Research Division, Joslin Diabetes Center, Boston, Massachusetts, USA
- Harvard Medical School, Boston, Massachusetts, USA
| | - Hamayle Saeed
- Research Division, Joslin Diabetes Center, Boston, Massachusetts, USA
- Harvard Medical School, Boston, Massachusetts, USA
| | - Christopher M. Mulla
- Research Division, Joslin Diabetes Center, Boston, Massachusetts, USA
- Harvard Medical School, Boston, Massachusetts, USA
| | - Hui Pan
- Research Division, Joslin Diabetes Center, Boston, Massachusetts, USA
| | - Jonathan M. Dreyfuss
- Research Division, Joslin Diabetes Center, Boston, Massachusetts, USA
- Harvard Medical School, Boston, Massachusetts, USA
| | - Donald C. Simonson
- Harvard Medical School, Boston, Massachusetts, USA
- Divsion of Endocrinology, Brigham and Women’s Hospital, Boston, Massachusetts, USA
| | - Darleen A. Sandoval
- Section of Nutrition, Department of Pediatrics, Division of Endocrinology, Diabetes, and Metabolism, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA
| | - Mary-Elizabeth Patti
- Research Division, Joslin Diabetes Center, Boston, Massachusetts, USA
- Harvard Medical School, Boston, Massachusetts, USA
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13
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Ramkumar R, Edge-Partington M, Terstege DJ, Adigun K, Ren Y, Khan NS, Rouhi N, Jamani NF, Tsutsui M, Epp JR, Sargin D. Long-Term Impact of Early-Life Stress on Serotonin Connectivity. Biol Psychiatry 2024; 96:287-299. [PMID: 38316332 DOI: 10.1016/j.biopsych.2024.01.024] [Citation(s) in RCA: 4] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/10/2023] [Revised: 01/04/2024] [Accepted: 01/19/2024] [Indexed: 02/07/2024]
Abstract
BACKGROUND Chronic childhood stress is a prominent risk factor for developing affective disorders, yet mechanisms underlying this association remain unclear. Maintenance of optimal serotonin (5-HT) levels during early postnatal development is critical for the maturation of brain circuits. Understanding the long-lasting effects of early-life stress (ELS) on serotonin-modulated brain connectivity is crucial to develop treatments for affective disorders arising from childhood stress. METHODS Using a mouse model of chronic developmental stress, we determined the long-lasting consequences of ELS on 5-HT circuits and behavior in females and males. Using FosTRAP mice, we cross-correlated regional c-Fos density to determine brain-wide functional connectivity of the raphe nucleus. We next performed in vivo fiber photometry to establish ELS-induced deficits in 5-HT dynamics and optogenetics to stimulate 5-HT release to improve behavior. RESULTS Adult female and male mice exposed to ELS showed heightened anxiety-like behavior. ELS further enhanced susceptibility to acute stress by disrupting the brain-wide functional connectivity of the raphe nucleus and the activity of 5-HT neuron population, in conjunction with increased orbitofrontal cortex (OFC) activity and disrupted 5-HT release in medial OFC. Optogenetic stimulation of 5-HT terminals in the medial OFC elicited an anxiolytic effect in ELS mice in a sex-dependent manner. CONCLUSIONS These findings suggest a significant disruption in 5-HT-modulated brain connectivity in response to ELS, with implications for sex-dependent vulnerability. The anxiolytic effect of the raphe-medial OFC circuit stimulation has potential implications for developing targeted stimulation-based treatments for affective disorders that arise from early life adversities.
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Affiliation(s)
- Raksha Ramkumar
- Department of Psychology, University of Calgary, Calgary, Alberta, Canada; Hotchkiss Brain Institute, University of Calgary, Calgary, Alberta, Canada; Alberta Children's Hospital Research Institute, University of Calgary, Calgary, Alberta, Canada
| | - Moriah Edge-Partington
- Department of Psychology, University of Calgary, Calgary, Alberta, Canada; Hotchkiss Brain Institute, University of Calgary, Calgary, Alberta, Canada; Alberta Children's Hospital Research Institute, University of Calgary, Calgary, Alberta, Canada
| | - Dylan J Terstege
- Hotchkiss Brain Institute, University of Calgary, Calgary, Alberta, Canada; Department of Cell Biology and Anatomy, University of Calgary, Calgary, Alberta, Canada; Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada
| | - Kabirat Adigun
- Hotchkiss Brain Institute, University of Calgary, Calgary, Alberta, Canada; Department of Cell Biology and Anatomy, University of Calgary, Calgary, Alberta, Canada; Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada
| | - Yi Ren
- Hotchkiss Brain Institute, University of Calgary, Calgary, Alberta, Canada; Department of Cell Biology and Anatomy, University of Calgary, Calgary, Alberta, Canada; Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada
| | - Nazmus S Khan
- Department of Psychology, University of Calgary, Calgary, Alberta, Canada; Hotchkiss Brain Institute, University of Calgary, Calgary, Alberta, Canada; Alberta Children's Hospital Research Institute, University of Calgary, Calgary, Alberta, Canada
| | - Nahid Rouhi
- Department of Psychology, University of Calgary, Calgary, Alberta, Canada; Hotchkiss Brain Institute, University of Calgary, Calgary, Alberta, Canada; Alberta Children's Hospital Research Institute, University of Calgary, Calgary, Alberta, Canada
| | - Naila F Jamani
- Department of Psychology, University of Calgary, Calgary, Alberta, Canada; Hotchkiss Brain Institute, University of Calgary, Calgary, Alberta, Canada; Alberta Children's Hospital Research Institute, University of Calgary, Calgary, Alberta, Canada
| | - Mio Tsutsui
- Department of Psychology, University of Calgary, Calgary, Alberta, Canada; Hotchkiss Brain Institute, University of Calgary, Calgary, Alberta, Canada; Alberta Children's Hospital Research Institute, University of Calgary, Calgary, Alberta, Canada
| | - Jonathan R Epp
- Hotchkiss Brain Institute, University of Calgary, Calgary, Alberta, Canada; Department of Cell Biology and Anatomy, University of Calgary, Calgary, Alberta, Canada; Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada
| | - Derya Sargin
- Department of Psychology, University of Calgary, Calgary, Alberta, Canada; Hotchkiss Brain Institute, University of Calgary, Calgary, Alberta, Canada; Alberta Children's Hospital Research Institute, University of Calgary, Calgary, Alberta, Canada; Department of Physiology and Pharmacology, University of Calgary, Calgary, Alberta, Canada.
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14
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Gmel AI, Mikko S, Ricard A, Velie BD, Gerber V, Hamilton NA, Neuditschko M. Using high-density SNP data to unravel the origin of the Franches-Montagnes horse breed. Genet Sel Evol 2024; 56:53. [PMID: 38987703 PMCID: PMC11238448 DOI: 10.1186/s12711-024-00922-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/22/2023] [Accepted: 07/03/2024] [Indexed: 07/12/2024] Open
Abstract
BACKGROUND The Franches-Montagnes (FM) is the last native horse breed of Switzerland, established at the end of the 19th century by cross-breeding local mares with Anglo-Norman stallions. We collected high-density SNP genotype data (Axiom™ 670 K Equine genotyping array) from 522 FM horses, including 44 old-type horses (OF), 514 European Warmblood horses (WB) from Sweden and Switzerland (including a stallion used for cross-breeding in 1990), 136 purebred Arabians (AR), 32 Shagya Arabians (SA), and 64 Thoroughbred (TB) horses, as introgressed WB stallions showed TB origin in their pedigrees. The aim of the study was to ascertain fine-scale population structures of the FM breed, including estimation of individual admixture levels and genomic inbreeding (FROH) by means of Runs of Homozygosity. RESULTS To assess fine-scale population structures within the FM breed, we applied a three-step approach, which combined admixture, genetic contribution, and FROH of individuals into a high-resolution network visualization. Based on this approach, we were able to demonstrate that population substructures, as detected by model-based clustering, can be either associated with a different genetic origin or with the progeny of most influential sires. Within the FM breed, admixed horses explained most of the genetic variance of the current breeding population, while OF horses only accounted for a small proportion of the variance. Furthermore, we illustrated that FM horses showed high TB admixture levels and we identified inconsistencies in the origin of FM horses descending from the Arabian stallion Doktryner. With the exception of WB, FM horses were less inbred compared to the other breeds. However, the relatively few but long ROH segments suggested diversity loss in both FM subpopulations. Genes located in FM- and OF-specific ROH islands had known functions involved in conformation and behaviour, two traits that are highly valued by breeders. CONCLUSIONS The FM remains the last native Swiss breed, clearly distinguishable from other historically introgressed breeds, but it suffered bottlenecks due to intensive selection of stallions, restrictive mating choices based on arbitrary definitions of pure breeding, and selection of rare coat colours. To preserve the genetic diversity of FM horses, future conservation managements strategies should involve a well-balanced selection of stallions (e.g., by integrating OF stallions in the FM breeding population) and avoid selection for rare coat colours.
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Affiliation(s)
- Annik Imogen Gmel
- Animal GenoPhenomics, Agroscope, Route de la Tioleyre 4, 1725, Posieux, Switzerland
- Equine Department, Vetsuisse Faculty, University of Zurich, Winterthurerstrasse 260, 8053, Zurich, Switzerland
| | - Sofia Mikko
- Department of Animal Breeding and Genetics, Swedish University of Agricultural Sciences, Box 7023, 750 07, Uppsala, Sweden
| | - Anne Ricard
- Institut National de la Recherche Agronomique, Domaine de Vilvert, 78350, Jouy-en-Josas, France
| | - Brandon D Velie
- Equine Genetics and Genomics Group, School of Life and Environmental Sciences, University of Sydney, RMC Gunn B19-603, Sydney, NSW, 2006, Australia
| | - Vinzenz Gerber
- Institut Suisse de Médecine Equine ISME, Vetsuisse Faculty, University of Bern, Länggassstrasse 124, 3012, Bern, Switzerland
| | - Natasha Anne Hamilton
- Sydney School of Veterinary Science, University of Sydney, Sydney, NSW, 2006, Australia
| | - Markus Neuditschko
- Animal GenoPhenomics, Agroscope, Route de la Tioleyre 4, 1725, Posieux, Switzerland.
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15
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Zhou J, Wu JW, Song BL, Jiang Y, Niu QH, Li LF, Liu YJ. 5-HT1A receptors within the intermediate lateral septum modulate stress vulnerability in male mice. Prog Neuropsychopharmacol Biol Psychiatry 2024; 132:110966. [PMID: 38354893 DOI: 10.1016/j.pnpbp.2024.110966] [Citation(s) in RCA: 2] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/30/2023] [Revised: 02/04/2024] [Accepted: 02/11/2024] [Indexed: 02/16/2024]
Abstract
Chronic stress is a major risk factor for psychiatric disorders. However, certain individuals may be at higher risk due to greater stress susceptibility. Elucidating the neurobiology of stress resilience and susceptibility may facilitate the development of novel strategies to prevent and treat stress-related disorders such as depression. Mounting evidence suggests that the serotonin (5-HT) system is a major regulator of stress sensitivity. In this study, we assessed the functions of 5-HT1A and 5-HT2A receptors within the lateral septum (LS) in regulating stress vulnerability. Among a group of male mice exposed to chronic social defeat stress (CSDS), 47.2% were classified as stress-susceptible, and these mice employed more passive coping strategies during the defeat and exhibited more severe anxiety- and depression-like behaviors during the following behavioral tests. These stress-susceptible mice also exhibited elevated neuronal activity in the LS as evidenced by greater c-Fos expression, greater activity of 5-HT neurons in both the dorsal and median raphe nucleus, and downregulated expression of the 5-HT1A receptor in the intermediate LS (LSi). Finally, we found the stress-induced social withdrawal symptoms could be rapidly relieved by LSi administration of 8-OH-DPAT, a 5-HT1A receptor agonist. These results indicate that 5-HT1A receptors within the LSi play an important role in stress vulnerability in mice. Therefore, modulation of stress vulnerable via 5-HT1A receptor activation in the LSi is a potential strategy to treat stress-related psychiatric disorders.
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Affiliation(s)
- Jie Zhou
- Research Center of Henan Provincial Agricultural Biomass Resource Engineering and Technology, College of Life Science and Agriculture, Nanyang Normal University, Nanyang 473061, China
| | - Jiao-Wen Wu
- Research Center of Henan Provincial Agricultural Biomass Resource Engineering and Technology, College of Life Science and Agriculture, Nanyang Normal University, Nanyang 473061, China
| | - Bai-Lin Song
- Research Center of Henan Provincial Agricultural Biomass Resource Engineering and Technology, College of Life Science and Agriculture, Nanyang Normal University, Nanyang 473061, China
| | - Yi Jiang
- Research Center of Henan Provincial Agricultural Biomass Resource Engineering and Technology, College of Life Science and Agriculture, Nanyang Normal University, Nanyang 473061, China
| | - Qiu-Hong Niu
- Research Center of Henan Provincial Agricultural Biomass Resource Engineering and Technology, College of Life Science and Agriculture, Nanyang Normal University, Nanyang 473061, China..
| | - Lai-Fu Li
- Research Center of Henan Provincial Agricultural Biomass Resource Engineering and Technology, College of Life Science and Agriculture, Nanyang Normal University, Nanyang 473061, China..
| | - Ying-Juan Liu
- Research Center of Henan Provincial Agricultural Biomass Resource Engineering and Technology, College of Life Science and Agriculture, Nanyang Normal University, Nanyang 473061, China..
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16
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Kaplan G. The evolution of social play in songbirds, parrots and cockatoos - emotional or highly complex cognitive behaviour or both? Neurosci Biobehav Rev 2024; 161:105621. [PMID: 38479604 DOI: 10.1016/j.neubiorev.2024.105621] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/14/2023] [Revised: 02/04/2024] [Accepted: 03/09/2024] [Indexed: 04/20/2024]
Abstract
Social play has been described in many animals. However, much of this social behaviour among birds, particularly in adults, is still relatively unexplored in terms of the environmental, psychological, and social dynamics of play. This paper provides an overview of what we know about adult social play in birds and addresses areas in which subtleties and distinctions, such as in play initiation and social organisation and its relationship to expressions of play, are considered in detail. The paper considers emotional, social, innovative, and cognitive aspects of play, then the environmental conditions and affiliative bonds, suggesting a surprisingly complex framework of criteria awaiting further research. Adult social play has so far been studied in only a small number of avian species, exclusively in those with a particularly large brain relative to body size without necessarily addressing brain functions and lateralization. When lateralization of brain function is considered, it can further illuminate a possibly significant relevance of play behaviour to the evolution of cognition, to management of emotions, and the development of sociality.
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Affiliation(s)
- Gisela Kaplan
- University of New England, Armidale, NSW, Australia.
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17
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Holanda VAD, de Almeida RN, de Oliveira MC, da Silva Junior ED, Galvão-Coelho NL, Calo' G, Ruzza C, Gavioli EC. Activation of NOP receptor increases vulnerability to stress: role of glucocorticoids and CRF signaling. Psychopharmacology (Berl) 2024; 241:1001-1010. [PMID: 38270614 DOI: 10.1007/s00213-024-06533-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/03/2023] [Accepted: 01/11/2024] [Indexed: 01/26/2024]
Abstract
RATIONALE Recently, we demonstrated that the activation of the nociceptin/orphanin FQ (N/OFQ) receptor (NOP) signaling facilitates depressive-like behaviors. Additionally, literature findings support the ability of the N/OFQ-NOP system to modulate the hypothalamic-pituitary-adrenal (HPA) axis. OBJECTIVES Considering that dysfunctional HPA axis is strictly related to stress-induced psychopathologies, we aimed to study the role of the HPA axis in the pro-depressant effects of NOP agonists. METHODS Mice were treated prior to stress with the NOP agonist Ro 65-6570, and immobility time in the forced swimming task and corticosterone levels were measured. Additionally, the role of endogenous glucocorticoids and CRF was investigated using the glucocorticoid receptor antagonist mifepristone and the CRF1 antagonist antalarmin in the mediation of the effects of Ro 65-6570. RESULTS The NOP agonist in a dose-dependent manner further increased the immobility of mice in the second swimming session compared to vehicle. By contrast, under the same conditions, the administration of the NOP antagonist SB-612111 before stress reduced immobility, while the antidepressant nortriptyline was inactive. Concerning in-serum corticosterone in mice treated with vehicle, nortriptyline, or SB-612111, a significant decrease was observed after re-exposition to stress, but no differences were detected in Ro 65-6570-treated mice. Administration of mifepristone or antalarmin blocked the Ro 65-6570-induced increase in the immobility time in the second swimming session. CONCLUSIONS Present findings suggest that NOP agonists increase vulnerability to depression by hyperactivating the HPA axis and then increasing stress circulating hormones and CRF1 receptor signaling.
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Affiliation(s)
- Victor A D Holanda
- Department of Biophysics and Pharmacology, Federal University of Rio Grande do Norte, Av. Senador salgado Filho, 3000, Campus Universitário - Lagoa Nova, Natal, 59078-900, Brazil
| | - Raissa N de Almeida
- Department of Physiology and Behavior and Postgraduate Program in Psychobiology, Federal University of Rio Grande do Norte, Natal, Brazil
| | - Matheus C de Oliveira
- Department of Biophysics and Pharmacology, Federal University of Rio Grande do Norte, Av. Senador salgado Filho, 3000, Campus Universitário - Lagoa Nova, Natal, 59078-900, Brazil
| | - Edilson D da Silva Junior
- Department of Biophysics and Pharmacology, Federal University of Rio Grande do Norte, Av. Senador salgado Filho, 3000, Campus Universitário - Lagoa Nova, Natal, 59078-900, Brazil
| | - Nicole L Galvão-Coelho
- Department of Physiology and Behavior and Postgraduate Program in Psychobiology, Federal University of Rio Grande do Norte, Natal, Brazil
| | - Girolamo Calo'
- Department of Pharmaceutical and Pharmacological Sciences, University of Padua, Padua, Italy
| | - Chiara Ruzza
- Department of Neuroscience and Rehabilitation, University of Ferrara, Ferrara, Italy
- LTTA Laboratory for Advanced Therapies, Technopole of Ferrara, Ferrara, Italy
| | - Elaine C Gavioli
- Department of Biophysics and Pharmacology, Federal University of Rio Grande do Norte, Av. Senador salgado Filho, 3000, Campus Universitário - Lagoa Nova, Natal, 59078-900, Brazil.
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18
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Bove M, Morgese MG, Dimonte S, Sikora V, Agosti LP, Palmieri MA, Tucci P, Schiavone S, Trabace L. Increased stress vulnerability in the offspring of socially isolated rats: Behavioural, neurochemical and redox dysfunctions. Prog Neuropsychopharmacol Biol Psychiatry 2024; 131:110945. [PMID: 38242425 DOI: 10.1016/j.pnpbp.2024.110945] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/28/2023] [Revised: 12/22/2023] [Accepted: 01/14/2024] [Indexed: 01/21/2024]
Abstract
Stressful events during pregnancy impact on the progeny neurodevelopment. However, little is known about preconceptional stress effects. The rat social isolation represents an animal model of chronic stress inducing a variety of dysfunctions. Moreover, social deprivation during adolescence interferes with key neurodevelopmental processes. Here, we investigated the development of behavioural, neurochemical and redox alterations in the male offspring of socially isolated female rats before pregnancy, reared in group (GRP) or in social isolation (ISO) from weaning until young-adulthood. To this aim, females were reared in GRP or in ISO conditions, from PND21 to PND70, when they were mated. Their male offspring was housed in GRP or ISO conditions through adolescence and until PND70, when passive avoidance-PA, novel object recognition-NOR and open field-OF tests were performed. Levels of noradrenaline (NA), serotonin (5-HT), 5-hydroxyindoleacetic acid (5-HIAA), glutamate (GLU) and GABA were assessed in the prefrontal cortex (PFC). Moreover, cortical ROS levels were quantified, as well as NF-kB and the NADPH oxidase NOX2 expression, redox status (expressed as GSH:GSSG ratio) and SOD1 amount. A significant decrease of the latency time in the PA was observed in the offspring of ISO females. In the NOR test, while a significant increase in the exploratory activity towards the novel object was observed in the offspring of GRP females, no significant differences were found in the offspring of ISO females. No significant differences were found in the OF test among experimental groups. Theoffspring of ISO females showed increased NA and 5-HIAA levels, whereas in the offspring persistently housed in isolation condition from weaninguntil adulthood, we detected reduced 5-HT levels and ehnanced 5-HIAA amount. No significant changes in GLU concentrations were detected, while decreased GABA content was observed in the offspring of ISO females exposed to social isolation. Increased ROS levels as well as reduced NF-κB, NOX2 expression were detected in the offspring of ISO females. This was accompanied by reduced redox status and enhanced SOD1 levels. In conclusion, our results suggest that female exposure to chronic social stress before pregnancy might have a profound influence on the offspring neurodevelopment in terms of cognitive, neurochemical and redox-related alterations, identifying this specific time window for possible preventive and therapeutic strategies.
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Affiliation(s)
- Maria Bove
- Department of Clinical and Experimental Medicine, University of Foggia, Via Napoli 20, Foggia 71122, Italy
| | - Maria Grazia Morgese
- Department of Clinical and Experimental Medicine, University of Foggia, Via Napoli 20, Foggia 71122, Italy
| | - Stefania Dimonte
- Department of Clinical and Experimental Medicine, University of Foggia, Via Napoli 20, Foggia 71122, Italy
| | - Vladyslav Sikora
- Department of Clinical and Experimental Medicine, University of Foggia, Via Napoli 20, Foggia 71122, Italy
| | - Lisa Pia Agosti
- Department of Clinical and Experimental Medicine, University of Foggia, Via Napoli 20, Foggia 71122, Italy
| | - Maria Adelaide Palmieri
- Department of Clinical and Experimental Medicine, University of Foggia, Via Napoli 20, Foggia 71122, Italy
| | - Paolo Tucci
- Department of Clinical and Experimental Medicine, University of Foggia, Via Napoli 20, Foggia 71122, Italy
| | - Stefania Schiavone
- Department of Clinical and Experimental Medicine, University of Foggia, Via Napoli 20, Foggia 71122, Italy.
| | - Luigia Trabace
- Department of Clinical and Experimental Medicine, University of Foggia, Via Napoli 20, Foggia 71122, Italy
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19
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Giunta S, Giordani C, De Luca M, Olivieri F. Long-COVID-19 autonomic dysfunction: An integrated view in the framework of inflammaging. Mech Ageing Dev 2024; 218:111915. [PMID: 38354789 DOI: 10.1016/j.mad.2024.111915] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/31/2023] [Revised: 02/05/2024] [Accepted: 02/09/2024] [Indexed: 02/16/2024]
Abstract
The recently identified syndrome known as Long COVID (LC) is characterized by a constellation of debilitating conditions that impair both physical and cognitive functions, thus reducing the quality of life and increasing the risk of developing the most common age-related diseases. These conditions are linked to the presence of symptoms of autonomic dysfunction, in association with low cortisol levels, suggestive of reduced hypothalamic-pituitary-adrenal (HPA) axis activity, and with increased pro-inflammatory condition. Alterations of dopamine and serotonin neurotransmitter levels were also recently observed in LC. Interestingly, at least some of the proposed mechanisms of LC development overlap with mechanisms of Autonomic Nervous System (ANS) imbalance, previously detailed in the framework of the aging process. ANS imbalance is characterized by a proinflammatory sympathetic overdrive, and a concomitant decreased anti-inflammatory vagal parasympathetic activity, associated with reduced anti-inflammatory effects of the HPA axis and cholinergic anti-inflammatory pathway (CAP). These neuro-immune-endocrine system imbalanced activities fuel the vicious circle of chronic inflammation, i.e. inflammaging. Here, we refine our original hypothesis that ANS dysfunction fuels inflammaging and propose that biomarkers of ANS imbalance could also be considered biomarkers of inflammaging, recognized as the main risk factor for developing age-related diseases and the sequelae of viral infections, i.e. LC.
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Affiliation(s)
- Sergio Giunta
- Casa di Cura Prof. Nobili (Gruppo Garofalo (GHC) Castiglione dei Pepoli -Bologna), Italy
| | - Chiara Giordani
- Clinic of Laboratory and Precision Medicine, IRCCS INRCA, Ancona, Italy.
| | - Maria De Luca
- Department of Nutrition Sciences, University of Alabama at Birmingham, Birmingham, AL 35294, USA
| | - Fabiola Olivieri
- Clinic of Laboratory and Precision Medicine, IRCCS INRCA, Ancona, Italy; Department of Clinical and Molecular Sciences, DISCLIMO, Università Politecnica delle Marche, Ancona, Italy
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20
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Antunes DF, Stettler PR, Taborsky B. The role of serotonin in modulating social competence in a cooperatively breeding fish. Behav Brain Res 2024; 461:114819. [PMID: 38141783 DOI: 10.1016/j.bbr.2023.114819] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/18/2023] [Revised: 12/14/2023] [Accepted: 12/16/2023] [Indexed: 12/25/2023]
Abstract
Behavioural interactions between conspecifics rely on the appreciation of social cues, which is achieved through biochemical switching of pre-existing neurophysiological pathways. Serotonin is one of the major neurotransmitters in the central nervous system responsible for the modulation of physiological and behavioural traits, in particular social behaviour. The relative importance of serotonin in modulating optimal social responses to the available social information (i.e., social competence) is yet unknown. Here we investigate how serotonin and the serotonin 1 A receptor (5-HT1A) modulate social competence in a competitive context. In the cooperatively breeding cichlid Neolamprologus pulcher, we pharmacologically manipulated the serotonin availability and 5-HT1A activity to test their effects on social behaviours during an asymmetric contest between the owner of a defended territory containing a shelter and an intruder devoid of a territory. In this contest, the adequate response by the intruders, the focal individuals in our study, is to show submissive behaviour in order to avoid eviction from the vicinity of the shelter. While the serotonin enhancer Fluoxetine did not affect the frequency of submission towards territory owners, reducing serotonin by a low dosage of 4-Chloro-DL-phenylalanine (PCPA) increased submissive behaviour. Furthermore, threat displays towards territory owners were reduced at high dosages of Fluoxetine and also at the lowest dosage of PCPA. 5-HT1A activation increased threat displays by intruders, indicating that this receptor may not be involved in regulating social competence. We conclude that serotonin, but not its receptor 5-HT1A plays an important role in the regulation of social competence.
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Affiliation(s)
- Diogo F Antunes
- Division of Behavioural Ecology, Institute of Ecology and Evolution, University of Bern, Wohlenstrasse 50A, 3032 Hinterkappelen, Switzerland; Laboratoire Évolution & Diversité Biologique (EDB UMR 5174), Université de Toulouse III, CNRS, IRD, UPS, 118 route de Narbonne, F-31062 Toulouse, France.
| | - Pia R Stettler
- Division of Behavioural Ecology, Institute of Ecology and Evolution, University of Bern, Wohlenstrasse 50A, 3032 Hinterkappelen, Switzerland
| | - Barbara Taborsky
- Division of Behavioural Ecology, Institute of Ecology and Evolution, University of Bern, Wohlenstrasse 50A, 3032 Hinterkappelen, Switzerland
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21
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Dong WL, Li YY, Zhang YM, Peng QW, Lu GL, Chen CR. Influence of childhood trauma on adolescent internet addiction: The mediating roles of loneliness and negative coping styles. World J Psychiatry 2023; 13:1133-1144. [PMID: 38186732 PMCID: PMC10768484 DOI: 10.5498/wjp.v13.i12.1133] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/23/2023] [Revised: 10/18/2023] [Accepted: 11/21/2023] [Indexed: 12/19/2023] Open
Abstract
BACKGROUND In the information age, the use of the internet and multimedia tools has large effects on the life of middle school students. Improper use of the internet may result in internet addiction (IA). Thus, actively exploring the factors influencing adolescent and the mechanism of addiction as well as promoting adolescent physical and mental health and academic development are priorities that families, schools, and society urgently need to address. AIM To explore the effect of childhood trauma on adolescent IA and to consider the roles of loneliness and negative coping styles. METHODS A total of 11310 students from six junior high schools in Henan, China, completed the child trauma questionnaire, IA test, loneliness scale, and simple coping style questionnaire. In addition, data were collected from 1044 adolescents with childhood trauma for analysis with IBM SPSS 26.0 and AMOS 28.0; we examined the relationships among childhood trauma, IA, loneliness, and negative coping styles. RESULTS We found that childhood trauma not only directly affected adolescents' IA but also affected IA through loneliness and negative coping styles. CONCLUSION Therefore, this study has theoretical implications regarding adolescent mental health and may inform interventions for IA.
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Affiliation(s)
- Wang-Lin Dong
- College of Nursing and Health, Institute of Nursing and Health, Henan University, Kaifeng 475000, Henan Province, China
| | - Yuan-Yuan Li
- College of Nursing and Health, Institute of Nursing and Health, Henan University, Kaifeng 475000, Henan Province, China
| | - Yi-Ming Zhang
- College of Nursing and Health, Institute of Nursing and Health, Henan University, Kaifeng 475000, Henan Province, China
| | - Qian-Wen Peng
- College of Nursing and Health, Institute of Nursing and Health, Henan University, Kaifeng 475000, Henan Province, China
| | - Guang-Li Lu
- School of Business, Institute of Business Administration, Henan University, Kaifeng 475000, Henan Province, China
| | - Chao-Ran Chen
- College of Nursing and Health, Institute of Nursing and Health, Henan University, Kaifeng 475000, Henan Province, China
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22
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Dong WY, Zhu X, Tang HD, Huang JY, Zhu MY, Cheng PK, Wang H, Wang XY, Wang H, Mao Y, Zhao W, Zhang Y, Tao WJ, Zhang Z. Brain regulation of gastric dysfunction induced by stress. Nat Metab 2023; 5:1494-1505. [PMID: 37592008 DOI: 10.1038/s42255-023-00866-z] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/10/2022] [Accepted: 07/18/2023] [Indexed: 08/19/2023]
Abstract
Psychological and physical stressors have been implicated in gastric disorders in humans. The mechanism coupling the brain to the stomach underlying stress-induced gastric dysfunction has remained elusive. Here, we show that the stomach directly receives acetylcholinergic inputs from the dorsal motor nucleus of the vagus (AChDMV), which are innervated by serotonergic neurons in the dorsal raphe nucleus (5-HTDRN). Microendoscopic calcium imaging and multi-tetrode electrophysiological recordings reveal that the 5-HTDRN → AChDMV → stomach circuit is inhibited with chronic stress accompanied by hypoactivate gastric function. Artificial activation of this circuit reverses the gastric dysfunction induced by chronic stress in both male and female mice. Our study demonstrates that this 5-HTDRN → AChDMV → stomach axis drives gastric dysfunction associated with stress, thus providing insights into the circuit basis for brain regulation of the stomach.
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Affiliation(s)
- Wan-Ying Dong
- Department of Anesthesiology, The First Affiliated Hospital of University of Science and Technology of China, Hefei National Laboratory for Physical Sciences at the Microscale, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, People's Republic of China
| | - Xia Zhu
- Department of Anesthesiology, The First Affiliated Hospital of University of Science and Technology of China, Hefei National Laboratory for Physical Sciences at the Microscale, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, People's Republic of China
| | - Hao-Di Tang
- Department of Anesthesiology, The First Affiliated Hospital of University of Science and Technology of China, Hefei National Laboratory for Physical Sciences at the Microscale, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, People's Republic of China
- Laboratory of Anesthesia and Critical Care Medicine, National-Local Joint Engineering Research Center of Translational Medicine of Anesthesiology, West China Hospital, Sichuan University, Chengdu, People's Republic of China
| | - Ji-Ye Huang
- Department of Anesthesiology, The First Affiliated Hospital of University of Science and Technology of China, Hefei National Laboratory for Physical Sciences at the Microscale, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, People's Republic of China
| | - Meng-Yu Zhu
- College & Hospital of Stomatology, Anhui Medical University, Key laboratory of Oral Diseases Research of Anhui Province, Hefei, People's Republic of China
- Department of Physiology, School of Basic Medical Sciences, Anhui Medical University, Hefei, People's Republic of China
| | - Ping-Kai Cheng
- Department of Anesthesiology, The First Affiliated Hospital of University of Science and Technology of China, Hefei National Laboratory for Physical Sciences at the Microscale, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, People's Republic of China
| | - Hao Wang
- School of Integrated Chinese and Western Medicine, Anhui University of Chinese Medicine, Hefei, People's Republic of China
| | - Xi-Yang Wang
- School of Integrated Chinese and Western Medicine, Anhui University of Chinese Medicine, Hefei, People's Republic of China
| | - Haitao Wang
- School of Integrated Chinese and Western Medicine, Anhui University of Chinese Medicine, Hefei, People's Republic of China
| | - Yu Mao
- Department of Anesthesiology, The First Affiliated Hospital of University of Science and Technology of China, Hefei National Laboratory for Physical Sciences at the Microscale, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, People's Republic of China
| | - Wan Zhao
- Department of Otolaryngology-Head and Neck Surgery, The First Affiliated Hospital of the University of Science and Technique of China, Hefei, People's Republic of China
| | - Yan Zhang
- Stroke Center and Department of Neurology, The First Affiliated Hospital of the University of Science and Technique of China, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, People's Republic of China
| | - Wen-Juan Tao
- College & Hospital of Stomatology, Anhui Medical University, Key laboratory of Oral Diseases Research of Anhui Province, Hefei, People's Republic of China.
- Department of Physiology, School of Basic Medical Sciences, Anhui Medical University, Hefei, People's Republic of China.
| | - Zhi Zhang
- Department of Anesthesiology, The First Affiliated Hospital of University of Science and Technology of China, Hefei National Laboratory for Physical Sciences at the Microscale, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, People's Republic of China.
- The Center for Advanced Interdisciplinary Science and Biomedicine, Institute of Health and Medicine, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, People's Republic of China.
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23
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Tortora F, Hadipour AL, Battaglia S, Falzone A, Avenanti A, Vicario CM. The Role of Serotonin in Fear Learning and Memory: A Systematic Review of Human Studies. Brain Sci 2023; 13:1197. [PMID: 37626553 PMCID: PMC10452575 DOI: 10.3390/brainsci13081197] [Citation(s) in RCA: 26] [Impact Index Per Article: 13.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/17/2023] [Revised: 08/07/2023] [Accepted: 08/08/2023] [Indexed: 08/27/2023] Open
Abstract
Fear is characterized by distinct behavioral and physiological responses that are essential for the survival of the human species. Fear conditioning (FC) serves as a valuable model for studying the acquisition, extinction, and expression of fear. The serotonin (5-hydroxytryptamine, 5-HT) system is known to play a significant role in emotional and motivational aspects of human behavior, including fear learning and expression. Accumulating evidence from both animal and human studies suggests that brain regions involved in FC, such as the amygdala, hippocampus, and prefrontal cortex, possess a high density of 5-HT receptors, implicating the crucial involvement of serotonin in aversive learning. Additionally, studies exploring serotonin gene polymorphisms have indicated their potential influence on FC. Therefore, the objective of this work was to review the existing evidence linking 5-HT with fear learning and memory in humans. Through a comprehensive screening of the PubMed and Web of Science databases, 29 relevant studies were included in the final review. These studies investigated the relationship between serotonin and fear learning using drug manipulations or by studying 5-HT-related gene polymorphisms. The results suggest that elevated levels of 5-HT enhance aversive learning, indicating that the modulation of serotonin 5-HT2A receptors regulates the expression of fear responses in humans. Understanding the role of this neurochemical messenger in associative aversive learning can provide insights into psychiatric disorders such as anxiety and post-traumatic stress disorder (PTSD), among others.
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Affiliation(s)
- Francesco Tortora
- Dipartimento di Scienze Cognitive, Psicologiche, Pedagogiche e Degli Studi Culturali, Università Degli Studi di Messina, Via Concezione 6, 98121 Messina, Italy; (F.T.); (A.F.)
| | - Abed L. Hadipour
- Dipartimento di Scienze Cognitive, Psicologiche, Pedagogiche e Degli Studi Culturali, Università Degli Studi di Messina, Via Concezione 6, 98121 Messina, Italy; (F.T.); (A.F.)
| | - Simone Battaglia
- Centro Studi e Ricerche in Neuroscienze Cognitive, Dipartimento di Psicologia “Renzo Canestrari”, Campus di Cesena, Alma Mater Studiorum Università di Bologna, Viale Rasi e Spinelli 176, 47521 Cesena, Italy;
| | - Alessandra Falzone
- Dipartimento di Scienze Cognitive, Psicologiche, Pedagogiche e Degli Studi Culturali, Università Degli Studi di Messina, Via Concezione 6, 98121 Messina, Italy; (F.T.); (A.F.)
| | - Alessio Avenanti
- Centro Studi e Ricerche in Neuroscienze Cognitive, Dipartimento di Psicologia “Renzo Canestrari”, Campus di Cesena, Alma Mater Studiorum Università di Bologna, Viale Rasi e Spinelli 176, 47521 Cesena, Italy;
- Centro de Investigación en Neuropsicología y Neurociencias Cognitivas, Universidad Católica Del Maule, Talca 3460000, Chile
| | - Carmelo M. Vicario
- Dipartimento di Scienze Cognitive, Psicologiche, Pedagogiche e Degli Studi Culturali, Università Degli Studi di Messina, Via Concezione 6, 98121 Messina, Italy; (F.T.); (A.F.)
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24
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Mihailova L, Shalabalija D, Zimmer A, Geskovski N, Makreski P, Petrushevska M, Simonoska Crcarevska M, Glavas Dodov M. Comparative Studies of the Uptake and Internalization Pathways of Different Lipid Nano-Systems Intended for Brain Delivery. Pharmaceutics 2023; 15:2082. [PMID: 37631296 PMCID: PMC10458318 DOI: 10.3390/pharmaceutics15082082] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/02/2023] [Revised: 07/14/2023] [Accepted: 08/01/2023] [Indexed: 08/27/2023] Open
Abstract
Lipid nano-systems were prepared and characterized in a series of well-established in vitro tests that could assess their interactions with the hCMEC/D3 and SH-SY5Y cell lines as a model for the blood-brain barrier and neuronal function, accordingly. The prepared formulations of nanoliposomes and nanostructured lipid carriers were characterized by z-average diameters of ~120 nm and ~105 nm, respectively, following a unimodal particle size distribution (PDI < 0.3) and negative Z-potential (-24.30 mV to -31.20 mV). Stability studies implied that the nano-systems were stable in a physiologically relevant medium as well as human plasma, except nanoliposomes containing poloxamer on their surface, where there was an increase in particle size of ~26%. The presence of stealth polymer tends to decrease the amount of adsorbed proteins onto a particle's surface, according to protein adsorption studies. Both formulations of nanoliposomes were characterized by a low cytotoxicity, while their cell viability was reduced when incubated with the highest concentration (100 μg/mL) of nanostructured lipid formulations, which could have been associated with the consumption of cellular energy, thus resulting in a reduction in metabolic active cells. The uptake of all the nano-systems in the hCMEC/D3 and SH-SY5Y cell lines was successful, most likely following ATP-dependent internalization, as well as transport via passive diffusion.
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Affiliation(s)
- Ljubica Mihailova
- Institute of Pharmaceutical Technology, Faculty of Pharmacy, Ss. Cyril and Methodius University in Skopje, Majka Tereza 47, 1000 Skopje, North Macedonia; (L.M.); (D.S.); (N.G.); (M.S.C.); (M.G.D.)
| | - Dushko Shalabalija
- Institute of Pharmaceutical Technology, Faculty of Pharmacy, Ss. Cyril and Methodius University in Skopje, Majka Tereza 47, 1000 Skopje, North Macedonia; (L.M.); (D.S.); (N.G.); (M.S.C.); (M.G.D.)
| | - Andreas Zimmer
- Department of Pharmaceutical Technology and Biopharmacy, Institute of Pharmaceutical Sciences, University of Graz, Universitatplatz 1/EG, A-8010 Graz, Austria
| | - Nikola Geskovski
- Institute of Pharmaceutical Technology, Faculty of Pharmacy, Ss. Cyril and Methodius University in Skopje, Majka Tereza 47, 1000 Skopje, North Macedonia; (L.M.); (D.S.); (N.G.); (M.S.C.); (M.G.D.)
| | - Petre Makreski
- Institute of Chemistry, Faculty of Natural Sciences and Mathematics, Ss. Cyril and Methodius University in Skopje, Arhimedova 5, 1000 Skopje, North Macedonia;
| | - Marija Petrushevska
- Institute of Pharmacology and Toxicology, Faculty of Medicine, Ss. Cyril and Methodius University in Skopje, 50 Divizija 6, 1000 Skopje, North Macedonia;
| | - Maja Simonoska Crcarevska
- Institute of Pharmaceutical Technology, Faculty of Pharmacy, Ss. Cyril and Methodius University in Skopje, Majka Tereza 47, 1000 Skopje, North Macedonia; (L.M.); (D.S.); (N.G.); (M.S.C.); (M.G.D.)
| | - Marija Glavas Dodov
- Institute of Pharmaceutical Technology, Faculty of Pharmacy, Ss. Cyril and Methodius University in Skopje, Majka Tereza 47, 1000 Skopje, North Macedonia; (L.M.); (D.S.); (N.G.); (M.S.C.); (M.G.D.)
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25
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Harris C, Kober KM, Paul SM, Cooper BA, Shin J, Oppegaard K, Morse L, Calvo-Schimmel A, Conley Y, Levine JD, Miaskowski C. Neurotransmitter Gene Polymorphisms Are Associated with Symptom Clusters in Patients Undergoing Radiation Therapy. Semin Oncol Nurs 2023; 39:151461. [PMID: 37419849 DOI: 10.1016/j.soncn.2023.151461] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/23/2023] [Revised: 05/22/2023] [Accepted: 05/24/2023] [Indexed: 07/09/2023]
Abstract
OBJECTIVES Purpose was to evaluate for associations between the severity of three distinct symptom clusters (ie, sickness-behavior, mood-cognitive, treatment-related) and polymorphisms for 16 genes involved in catecholaminergic, GABAergic, and serotonergic neurotransmission. DATA SOURCES Patients with breast and prostate cancer (n = 157) completed study questionnaires at the completion of radiation therapy. Memorial Symptom Assessment Scale was used to assess the severity of 32 common symptoms. Three distinct symptom clusters were identified using exploratory factor analysis. Associations between the symptom cluster severity scores and neurotransmitter gene polymorphisms were evaluated using regression analyses. CONCLUSION Severity scores for the sickness-behavior symptom cluster were associated with polymorphisms for solute carrier family 6 (SLC6A) member 2 (SLC6A2), SLC6A3, SLC6A1, and 5-hydroxytryptamine receptor (HTR) 2A (HTR2A) genes. For the mood-cognitive symptom cluster, severity scores were associated with polymorphisms for adrenoreceptor alpha 1D, SLC6A2, SLC6A3, SLC6A1, HTR2A, and HTR3A. Severity scores for the treatment-related symptom cluster were associated with polymorphisms for SLC6A2, SLC6A3, catechol-o-methyltransferase, SLC6A1, HTR2A, SLC6A4, and tryptophan hydroxylase 2. IMPLICATIONS FOR NURSING PRACTICE Findings suggest that polymorphisms for several neurotransmitter genes are involved in the severity of sickness-behavior, mood-cognitive, and treatment-related symptom clusters in oncology patients at the completion of radiation therapy. Four genes with various associated polymorphisms were common across the three distinct symptom clusters (ie, SLC6A2, SLC6A3, SLC6A1, HTR2A) which suggest that these clusters have common underlying mechanisms.
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Affiliation(s)
- Carolyn Harris
- Department of Health Promotion and Development, School of Nursing, University of Pittsburgh, Pittsburgh, Pennsylvania
| | - Kord M Kober
- Department of Physiological Nursing, School of Nursing, University of California, San Francisco, California
| | - Steven M Paul
- Department of Physiological Nursing, School of Nursing, University of California, San Francisco, California
| | - Bruce A Cooper
- Department of Physiological Nursing, School of Nursing, University of California, San Francisco, California
| | - Joosun Shin
- Department of Physiological Nursing, School of Nursing, University of California, San Francisco, California
| | - Kate Oppegaard
- Department of Physiological Nursing, School of Nursing, University of California, San Francisco, California
| | - Lisa Morse
- Department of Physiological Nursing, School of Nursing, University of California, San Francisco, California
| | - Alejandra Calvo-Schimmel
- Department of Physiological Nursing, School of Nursing, University of California, San Francisco, California
| | - Yvette Conley
- Department of Health Promotion and Development, School of Nursing, University of Pittsburgh, Pittsburgh, Pennsylvania
| | - Jon D Levine
- Department of Medicine, School of Nursing and School of Medicine, University of California, San Francisco, California
| | - Christine Miaskowski
- Department of Physiological Nursing, School of Nursing, University of California, San Francisco, California.
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26
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Rastoldo G, Tighilet B. Thyroid Axis and Vestibular Physiopathology: From Animal Model to Pathology. Int J Mol Sci 2023; 24:9826. [PMID: 37372973 DOI: 10.3390/ijms24129826] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/07/2023] [Revised: 06/02/2023] [Accepted: 06/03/2023] [Indexed: 06/29/2023] Open
Abstract
A recent work of our group has shown the significant effects of thyroxine treatment on the restoration of postural balance function in a rodent model of acute peripheral vestibulopathy. Based on these findings, we attempt to shed light in this review on the interaction between the hypothalamic-pituitary-thyroid axis and the vestibular system in normal and pathological situations. Pubmed database and relevant websites were searched from inception through to 4 February 2023. All studies relevant to each subsection of this review have been included. After describing the role of thyroid hormones in the development of the inner ear, we investigated the possible link between the thyroid axis and the vestibular system in normal and pathological conditions. The mechanisms and cellular sites of action of thyroid hormones on animal models of vestibulopathy are postulated and therapeutic options are proposed. In view of their pleiotropic action, thyroid hormones represent a target of choice to promote vestibular compensation at different levels. However, very few studies have investigated the relationship between thyroid hormones and the vestibular system. It seems then important to more extensively investigate the link between the endocrine system and the vestibule in order to better understand the vestibular physiopathology and to find new therapeutic leads.
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Affiliation(s)
- Guillaume Rastoldo
- Aix Marseille Université-CNRS, Laboratoire de Neurosciences Cognitives, LNC UMR 7291, 13331 Marseille, France
| | - Brahim Tighilet
- Aix Marseille Université-CNRS, Laboratoire de Neurosciences Cognitives, LNC UMR 7291, 13331 Marseille, France
- GDR Vertige CNRS Unité GDR2074, 13331 Marseille, France
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27
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Intui K, Nuchniyom P, Laoung-on J, Jaikang C, Quiggins R, Sudwan P. Neuroprotective Effect of White Nelumbo nucifera Gaertn. Petal Tea in Rats Poisoned with Mancozeb. Foods 2023; 12:2175. [PMID: 37297420 PMCID: PMC10252518 DOI: 10.3390/foods12112175] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/25/2023] [Revised: 05/24/2023] [Accepted: 05/26/2023] [Indexed: 06/12/2023] Open
Abstract
Nelumbo nucifera Gaertn. (N. nucifera) tea is used as food and folk medicine to reduce toxicity in Southeast Asia. Mancozeb (Mz) is used for controlling fungi in agriculture and contains heavy metals. This study aimed to examine the effect of white N. nucifera petal tea on cognitive behavior, hippocampus histology, oxidative stress, and amino acid metabolism in rats poisoned with mancozeb. Seventy-two male Wistar rats were divided into nine groups (n = 8 in each). Y-maze spontaneous alternation test was used to assess cognitive behavior, and amino acid metabolism was investigated by nuclear magnetic resonance spectroscopy (1H-NMR) from blood. There was a significant increase in relative brain weight in the Mz co-administered with the highest dose (2.20 mg/kg bw) of white N. nucifera group. The levels of tryptophan, kynurenine, picolinic acid, and serotonin in blood showed a significant decrease in the Mz group and a significant increase in the Mz co-administered with low dose (0.55 mg/kg bw) of white N. nucifera group. However, there was no significant difference in cognitive behavior, hippocampus histology, oxidative stress, and corticosterone. This study demonstrated that a low dose of white N. nucifera petal tea has a neuroprotective effect against mancozeb.
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Affiliation(s)
- Ketsarin Intui
- Department of Anatomy, Faculty of Medicine, Chiang Mai University, Chiang Mai 50200, Thailand; (K.I.)
| | - Pimchanok Nuchniyom
- Department of Anatomy, Faculty of Medicine, Chiang Mai University, Chiang Mai 50200, Thailand; (K.I.)
| | - Jiraporn Laoung-on
- Department of Anatomy, Faculty of Medicine, Chiang Mai University, Chiang Mai 50200, Thailand; (K.I.)
| | - Churdsak Jaikang
- Toxicology Section, Department of Forensic Medicine, Faculty of Medicine, Chiang Mai University, Chiang Mai 50200, Thailand
| | - Ranida Quiggins
- Department of Anatomy, Faculty of Medicine, Chiang Mai University, Chiang Mai 50200, Thailand; (K.I.)
| | - Paiwan Sudwan
- Department of Anatomy, Faculty of Medicine, Chiang Mai University, Chiang Mai 50200, Thailand; (K.I.)
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28
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Yu F, Hou ZS, Luo HR, Li HX, Cui XF, Li JL, Feng WR, Tang YK, Su SY, Gao QF, Xiao J, Xu P. Neurobehavioral disorders induced by environmental zinc in female zebrafish (Danio rerio): Insights from brain and intestine transcriptional and metabolic signatures. CHEMOSPHERE 2023:138962. [PMID: 37230304 DOI: 10.1016/j.chemosphere.2023.138962] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/05/2023] [Revised: 04/26/2023] [Accepted: 05/15/2023] [Indexed: 05/27/2023]
Abstract
Human activities can cause zinc (Zn) contamination of aquatic environments. Zn is an essential trace metal, but effects of environmentally relevant Zn exposure on the brain-intestine axis in fish are poorly understood. Here, six-month-old female zebrafish (Danio rerio) were exposed to environmentally relevant Zn concentrations (0, 1.0, and 1.5 mg/L) for six weeks. Zn significantly accumulated in the brain and intestine, causing anxiety-like behaviors and altered social behaviors. Zn accumulation altered levels of neurotransmitters, including serotonin, glutamate, and γ-aminobutyric acid, in the brain and intestine, and these changes were directly associated with changes in behavior. Zn caused oxidative damage and mitochondrial dysfunction, and impaired NADH dehydrogenase, thereby dysregulating the energy supply in brain Zn exposure resulted in nucleotide imbalance and dysregulation of DNA replication and the cell cycle, potentially impairing the self-renewal of intestinal cells. Zn also disturbed carbohydrate and peptide metabolism in the intestine. These results indicate that chronic exposure to Zn at environmentally relevant concentrations dysregulates the bidirectional interaction of the brain-intestine axis with respect to neurotransmitters, nutrients, and nucleotide metabolites, thereby causing neurological disorder-like behaviors. Our study highlights the necessity to evaluate the negative impacts of chronic environmentally relevant Zn exposure on the health of humans and aquatic animals.
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Affiliation(s)
- Fan Yu
- Key Laboratory of Freshwater Fisheries and Germplasm Resources Utilization, Ministry of Agriculture and Rural Affairs, Freshwater Fisheries Research Center, Chinese Academy of Fishery Sciences, Wuxi, 214081, China.
| | - Zhi-Shuai Hou
- Key Laboratory of Mariculture (Ocean University of China), Ministry of Education (KLMME), Ocean University of China, Qingdao, 266003, China
| | - Hong-Rui Luo
- State Key Laboratory of Freshwater Ecology and Biotechnology, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan, 430072, China
| | - Hong-Xia Li
- Key Laboratory of Freshwater Fisheries and Germplasm Resources Utilization, Ministry of Agriculture and Rural Affairs, Freshwater Fisheries Research Center, Chinese Academy of Fishery Sciences, Wuxi, 214081, China
| | - Xue-Fan Cui
- State Key Laboratory of Freshwater Ecology and Biotechnology, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan, 430072, China
| | - Jian-Lin Li
- Key Laboratory of Freshwater Fisheries and Germplasm Resources Utilization, Ministry of Agriculture and Rural Affairs, Freshwater Fisheries Research Center, Chinese Academy of Fishery Sciences, Wuxi, 214081, China
| | - Wen-Rong Feng
- Key Laboratory of Freshwater Fisheries and Germplasm Resources Utilization, Ministry of Agriculture and Rural Affairs, Freshwater Fisheries Research Center, Chinese Academy of Fishery Sciences, Wuxi, 214081, China
| | - Yong-Kai Tang
- Key Laboratory of Freshwater Fisheries and Germplasm Resources Utilization, Ministry of Agriculture and Rural Affairs, Freshwater Fisheries Research Center, Chinese Academy of Fishery Sciences, Wuxi, 214081, China
| | - Sheng-Yan Su
- Key Laboratory of Freshwater Fisheries and Germplasm Resources Utilization, Ministry of Agriculture and Rural Affairs, Freshwater Fisheries Research Center, Chinese Academy of Fishery Sciences, Wuxi, 214081, China
| | - Qin-Feng Gao
- Key Laboratory of Mariculture (Ocean University of China), Ministry of Education (KLMME), Ocean University of China, Qingdao, 266003, China
| | - Jun Xiao
- Key Laboratory of Comprehensive Development and Utilization of Aquatic Germplasm Resources of China (Guangxi) and ASEAN (Co-construction by Ministry and Province), China of Fishery Sciences, Nanning, 530021, China.
| | - Pao Xu
- Key Laboratory of Freshwater Fisheries and Germplasm Resources Utilization, Ministry of Agriculture and Rural Affairs, Freshwater Fisheries Research Center, Chinese Academy of Fishery Sciences, Wuxi, 214081, China.
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Puchner E, Platzer M, Dalkner N, Schwalsberger K, Lenger M, Fellendorf FT, Unterrainer HF, Schwerdtfeger A, Reininghaus B, Reininghaus EZ. Effects of Metabolic Syndrome and Sex on Stress Coping Strategies in Individuals with Depressive Disorder. Metabolites 2023; 13:metabo13050652. [PMID: 37233693 DOI: 10.3390/metabo13050652] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/27/2023] [Revised: 04/26/2023] [Accepted: 05/08/2023] [Indexed: 05/27/2023] Open
Abstract
Metabolic syndrome (MetS) is related to depression and contributes to reduced life expectancy in individuals with mental disorders. Stress coping strategies are important factors in the development and maintenance of depressive disorders and have been related to metabolic disturbances. The aim of this study was to determine whether there is a difference in the use of positive (re- and devaluation, distraction, and control) and negative stress coping strategies in relation to patients' MetS. A sample of 363 individuals (n female = 204, n male = 159) with a diagnosis of depression was measured with the Stress Coping Style Questionnaire and the Beck Depression Inventory. In addition, we collected data on MetS (waist circumference, triglycerides, high-density lipoprotein, fasting glucose/diabetes, blood pressure/hypertonia) according to the International Diabetes Federation. A 2 × 2 design including Mets (with vs. without) and sex (female vs. male) was performed to test for differences in stress coping strategies. Individuals with depression and MetS scored higher on distraction strategies than depressed individuals without MetS (p < 0.01, corrected with false discovery rate). In addition, we found sex differences in stress coping strategies indicating that women with depression scored higher on distraction strategies (p < 0.001, FDR corrected), as well as negative strategies (p < 0.001, FDR corrected), than men. No significant interaction between MetS and sex was found regarding the higher value of stress coping strategies. Findings suggest that individuals with depression and MetS used distraction strategies to a higher amount to cope with stress, which could be stress eating in some cases, than those without MetS. Women with depressive disorders had higher values than men on other coping strategies in our sample of individuals with depression. A better understanding of MetS and sex-specific differences in stress coping strategies might help to plan more effective preventive strategies and personalized treatment options for depression.
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Affiliation(s)
- Eva Puchner
- Institute of Psychology, University of Graz, 8010 Graz, Austria
| | - Martina Platzer
- Department of Psychiatry and Psychotherapeutic Medicine, Medical University Graz, 8036 Graz, Austria
| | - Nina Dalkner
- Department of Psychiatry and Psychotherapeutic Medicine, Medical University Graz, 8036 Graz, Austria
| | - Karin Schwalsberger
- Department of Psychiatry and Psychotherapeutic Medicine, Medical University Graz, 8036 Graz, Austria
| | - Melanie Lenger
- Department of Psychiatry and Psychotherapeutic Medicine, Medical University Graz, 8036 Graz, Austria
| | - Frederike T Fellendorf
- Department of Psychiatry and Psychotherapeutic Medicine, Medical University Graz, 8036 Graz, Austria
| | - Human-Friedrich Unterrainer
- Institute of Psychology, University of Graz, 8010 Graz, Austria
- Department of Psychiatry and Psychotherapeutic Medicine, Medical University Graz, 8036 Graz, Austria
- Institute of Religious Studies, University of Vienna, 1010 Vienna, Austria
- Center for Integrative Addiction Research (CIAR), Grüner Kreis Society, 1110 Vienna, Austria
- Faculty of Psychotherapy Science, Sigmund Freud University, 1020 Vienna, Austria
| | | | - Bernd Reininghaus
- Department of Psychiatry and Psychotherapeutic Medicine, Medical University Graz, 8036 Graz, Austria
| | - Eva Z Reininghaus
- Department of Psychiatry and Psychotherapeutic Medicine, Medical University Graz, 8036 Graz, Austria
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Bottini CLJ, MacDougall-Shackleton SA. Methylmercury effects on avian brains. Neurotoxicology 2023; 96:140-153. [PMID: 37059311 DOI: 10.1016/j.neuro.2023.04.004] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/22/2023] [Revised: 04/03/2023] [Accepted: 04/11/2023] [Indexed: 04/16/2023]
Abstract
Methylmercury (MeHg) is a concerning contaminant due to its ubiquity and harmful effects on organisms. Although birds are important models in the neurobiology of vocal learning and adult neuroplasticity, the neurotoxic effects of MeHg are less understood in birds than mammals. We surveyed the literature on MeHg effects on biochemical changes in the avian brain. Publication rates of papers related to neurology and/or birds and/or MeHg increased with time and can be linked with historical events, regulations, and increased understanding of MeHg cycling in the environment. However, publications on MeHg effects on the avian brain remain relatively low across time. The neural effects measured to evaluate MeHg neurotoxicity in birds changed with time and researcher interest. The measures most consistently affected by MeHg exposure in birds were markers of oxidative stress. NMDA, acetylcholinesterase, and Purkinje cells also seem sensitive to some extent. MeHg exposure has the potential to affect most neurotransmitter systems but more studies are needed for validation in birds. We also review the main mechanisms of MeHg-induced neurotoxicity in mammals and compare it to what is known in birds. The literature on MeHg effects on the avian brain is limited, preventing full construction of an adverse outcome pathway. We identify research gaps for taxonomic groups such as songbirds, and age- and life-stage groups such as immature fledgling stage and adult non-reproductive life stage. In addition, results are often inconsistent between experimental and field studies. We conclude that future neurotoxicological studies of MeHg impacts on birds need to better connect the numerous aspects of exposure from molecular physiological effects to behavioural outcomes that would be ecologically or biologically relevant for birds, especially under challenging conditions.
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Affiliation(s)
- Claire L J Bottini
- University of Western Ontario, Department of Biology, 1151 Richmond St., London Ontario, N6A 5B7; Advanced Facility for Avian Research, University of Western Ontario, London, Ontario, Canada.
| | - Scott A MacDougall-Shackleton
- Advanced Facility for Avian Research, University of Western Ontario, London, Ontario, Canada; University of Western Ontario, Department of Psychology, 1151 Richmond St., London Ontario, N6A 5C2
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Kang JWM, Keay KA, Kendig MD, Corbit LH, Mor D. Serotonin and Dopamine Show Different Response Profiles to Acute Stress in the Nucleus Accumbens and Medial Prefrontal Cortex of Rats with Neuropathic Pain. Neurochem Res 2023; 48:2265-2280. [PMID: 36941432 PMCID: PMC10182167 DOI: 10.1007/s11064-023-03906-y] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/18/2022] [Revised: 02/23/2023] [Accepted: 03/03/2023] [Indexed: 03/23/2023]
Abstract
The ability to adaptively guide behaviour requires the integration of external information with internal motivational factors. Decision-making capabilities can be impaired by acute stress and is often exacerbated by chronic pain. Chronic neuropathic pain patients often present with cognitive dysfunction, including impaired decision-making. The mechanisms underlying these changes are not well understood but may include altered monoaminergic transmission in the brain. In this study we investigated the relationships between dopamine, serotonin, and their metabolites in key brain regions that regulate motivated behaviour and decision-making. The neurochemical profiles of the medial prefrontal cortex, orbital prefrontal cortex, and nucleus accumbens were analysed using HPLC in rats that received a chronic constriction injury (CCI) of the right sciatic nerve and an acute stress (15-min restraint), prior to an outcome devaluation task. CCI alone significantly decreased dopamine but not serotonin concentrations in the medial prefrontal cortex. By contrast, restraint stress acutely increased dopamine in the medial prefrontal cortex, and the nucleus accumbens; and increased serotonin in the medial prefrontal cortex 2 h later. The sustained dopaminergic and serotonergic responses to acute stress highlight the importance of an animal's ability to mount an effective coping response. In addition, these data suggest that the impact of nerve injury and acute stress on outcome-devaluation occurs independently of dopaminergic and serotonergic transmission in the medial prefrontal cortex, orbital prefrontal cortex and nucleus accumbens of rats.
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Affiliation(s)
- James W M Kang
- School of Medical Sciences [Neuroscience], The University of Sydney, Sydney, NSW, 2006, Australia.
| | - Kevin A Keay
- School of Medical Sciences [Neuroscience], The University of Sydney, Sydney, NSW, 2006, Australia
| | - Michael D Kendig
- School of Life Sciences, University of Technology Sydney, Sydney, NSW, 2007, Australia
| | - Laura H Corbit
- Department of Psychology, The University of Toronto, Toronto, ON, M5S 3G3, Canada
| | - David Mor
- School of Medical Sciences [Neuroscience], The University of Sydney, Sydney, NSW, 2006, Australia
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Raeeszadeh M, Khalili T, Sharifi H, Mohammadzadeh P. Ameliorative effect of Brassica oleracea var. Italica extract on oxidative damage of arsenic in the rat's brain: biochemical, pathological, and behavioral aspects. Metab Brain Dis 2023; 38:1323-1334. [PMID: 36701015 DOI: 10.1007/s11011-023-01164-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/20/2022] [Accepted: 01/12/2023] [Indexed: 01/27/2023]
Abstract
Brain damage caused by the metal accumulation may result in the permanent injuries including severe neurological disorders. Thus, the aim of this study was to determine the medicinal efficacy of broccoli extract in arsenic-induced brain poisoning. Twenty-eight female rats were classified into 4 groups; control, receiving sodium arsenate (As), As + broccoli extract (As + Bc), and (Bc). Then, the Elevated Plus-Maze and pathological-biochemical assessment of the brain tissue were performed. Moreover, the GC-MS was used to explore the quantity and quality of broccoli extract. The catalase had a significant decrease in the As group compared to that of the control group; As + Bc and Bc groups also showed a significant increase compared to that of the As group. Glutathione peroxidase was the lowest in the As group (1.84 ± 0.97) and the highest in the Bc group (5.51 ± 2.31). The Treatment significantly reduced pro-inflammatory cytokines in the As + Bc group. In addition, in terms of behavioral changes, the duration of presence in the open arm was reduced in the As group compared to that of the control group. Besides, the open arm duration increased significantly in the Bc group. Interestingly, there was a significant increase in estrogen and gonadotropin hormones in the Bc group compared to the other groups. Pathological findings showed that the condition of cortical neurons was improved and the surrounding space was reduced in As + Bc compared to that of the As group. In addition, more than 30% of the extract's compounds are made up Phytol,1-isothiocyanate-4-[methylsulfinyl] butane, and γ-Sitosterol. Thereby, the broccoli extract with active substances was highly effective in enhancing the behavioral and pathological parameters switch in rats with arsenic-induced poisoned brains.
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Affiliation(s)
- Mahdieh Raeeszadeh
- Department of Basic Sciences, Sanandaj Branch, Islamic Azad University, Sanandaj, Iran.
| | - Tabasom Khalili
- Graduate of Faculty of Veterinary Sciences, Sanandaj Branch, Islamic Azad University, Sanandaj, Iran
| | - Hanieh Sharifi
- Graduate of Faculty of Veterinary Sciences, Sanandaj Branch, Islamic Azad University, Sanandaj, Iran
| | - Peyman Mohammadzadeh
- Department of Pathobiology Sciences, Sanandaj Branch, Islamic Azad University, Sanandaj, Iran
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García-Gutiérrez MS, Navarro D, Austrich-Olivares A, Manzanares J. Unveiling behavioral and molecular neuroadaptations related to the antidepressant action of cannabidiol in the unpredictable chronic mild stress model. Front Pharmacol 2023; 14:1171646. [PMID: 37144214 PMCID: PMC10151764 DOI: 10.3389/fphar.2023.1171646] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/22/2023] [Accepted: 04/03/2023] [Indexed: 05/06/2023] Open
Abstract
Introduction: This study aims to further characterize cannabidiol's pharmacological and molecular profile as an antidepressant. Methods: Effects of cannabidiol (CBD), alone or combined with sertraline (STR), were evaluated in male CD1 mice (n = 48) exposed to an unpredictable chronic mild stress (UCMS) procedure. Once the model was established (4 weeks), mice received CBD (20 mg·kg-1, i.p.), STR (10 mg·kg-1, p.o.) or its combination for 28 days. The efficacy of CBD was evaluated using the light-dark box (LDB), elevated plus maze (EPM), tail suspension (TS), sucrose consumption (SC) and novel object recognition (NOR) tests. Gene expression changes in the serotonin transporter, 5-HT1A and 5-HT2A receptors, BDNF, VGlut1 and PPARdelta, were evaluated in the dorsal raphe, hippocampus (Hipp) and amygdala by real-time PCR. Besides, BDNF, NeuN and caspase-3 immunoreactivity were assessed in the Hipp. Results: CBD exerted anxiolytic and antidepressant-like effects at 4 and 7 days of treatment in the LDB and TS tests, respectively. In contrast, STR required 14 days of treatment to show efficacy. CBD improved cognitive impairment and anhedonia more significantly than STR. CBD plus STR showed a similar effect than CBD in the LBD, TST and EPM. However, a worse outcome was observed in the NOR and SI tests. CBD modulates all molecular disturbances induced by UCMS, whereas STR and the combination could not restore 5-HT1A, BDNF and PPARdelta in the Hipp. Discussion: These results pointed out CBD as a potential new antidepressant with faster action and efficiency than STR. Particular attention should be given to the combination of CBD with current SSRI since it appears to produce a negative impact on treatment.
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Affiliation(s)
- María Salud García-Gutiérrez
- Instituto de Neurociencias, Universidad Miguel Hernández, Alicante, Spain
- Research Network on Primary Addictions, Instituto de Salud Carlos III, MICINN and FEDER, Madrid, Spain
- Instituto de Investigación Sanitaria y Biomédica de Alicante (ISABIAL), Alicante, Spain
| | - Daniela Navarro
- Instituto de Neurociencias, Universidad Miguel Hernández, Alicante, Spain
- Research Network on Primary Addictions, Instituto de Salud Carlos III, MICINN and FEDER, Madrid, Spain
- Instituto de Investigación Sanitaria y Biomédica de Alicante (ISABIAL), Alicante, Spain
| | | | - Jorge Manzanares
- Instituto de Neurociencias, Universidad Miguel Hernández, Alicante, Spain
- Research Network on Primary Addictions, Instituto de Salud Carlos III, MICINN and FEDER, Madrid, Spain
- Instituto de Investigación Sanitaria y Biomédica de Alicante (ISABIAL), Alicante, Spain
- *Correspondence: Jorge Manzanares,
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Sbragaglia V, Roy T, Thörnqvist PO, López-Olmeda JF, Winberg S, Arlinghaus R. Evolutionary implications of size-selective mortality on the ontogenetic development of shoal cohesion: a neurochemical approach using a zebrafish, Danio rerio, harvest selection experiment. Behav Ecol Sociobiol 2022. [DOI: 10.1007/s00265-022-03258-7] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/09/2022]
Abstract
Abstract
Size-selective mortality may evolutionarily alter life-history as well as individual behavioral and physiological traits. Moreover, size-selective mortality can affect group behavioral traits, such as shoaling and collective properties (e.g., shoal cohesion), which are relevant for finding food and reducing risk of predation. Here, we present experimental evidence using selection lines of zebrafish (Danio rerio) that were exposed to positive (large-harvested), negative (small-harvested), and random (control) size-selective mortality for five generations, followed by eight generations during which harvesting was halted to remove maternal effects and to study evolutionarily fixed outcomes. We investigated changes in shoal cohesion and turnover in monoamines in zebrafish through ontogeny. To that end, we repeatedly measured inter-individual distance in groups of eight fish and the turnovers of dopamine and serotonin in brains of fish from juvenile to the adult stage at 40-day intervals. We, firstly, found that shoal cohesion was overall consistent through ontogeny at group levels suggesting the presence of collective personality. Secondly, we found a decrease in shoal cohesion through ontogeny in the small-harvested and control lines, while the large-harvested line did not show any ontogenetic change. Thirdly, the selection lines did not differ among each other in shoal cohesion at any ontogenetic stage. Fourthly, dopamine turnover increased through ontogeny in a similar way for all lines while the serotonin turnover decreased in the large-harvested and control lines, but not in the small-harvested line. The large-harvested line also had higher serotonin turnover than controls at specific time periods. In conclusion, intensive size-selective mortality left an evolutionary legacy of asymmetric selection responses in the ontogeny of shoal cohesion and the underlying physiological mechanisms in experimentally harvested zebrafish in the laboratory.
Significant statement
The evolution of animal behavior can be affected by human activities both at behavioral and physiological levels, but causal evidence is scarce and mostly focusing on single life-stages. We studied whether and to what extent size-selective harvesting, a common selection pattern in fisheries, can be an evolutionary driver of the development of shoal cohesion during ontogeny. We used a multi-generation experiment with zebrafish to study cause-and-effects of opposing size-selection patterns. We quantified shoal cohesion, and serotonin and dopamine turnover in the brain. We found that shoal cohesion emerged as a collective personality trait and that behavioral and physiological responses were asymmetrical with respect to the opposing selection patterns.
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Shine JM, O’Callaghan C, Walpola IC, Wainstein G, Taylor N, Aru J, Huebner B, John YJ. Understanding the effects of serotonin in the brain through its role in the gastrointestinal tract. Brain 2022; 145:2967-2981. [DOI: 10.1093/brain/awac256] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/23/2022] [Revised: 06/12/2022] [Accepted: 06/14/2022] [Indexed: 11/12/2022] Open
Abstract
Abstract
The neuromodulatory arousal system imbues the nervous system with the flexibility and robustness required to facilitate adaptive behaviour. While there are well-understood mechanisms linking dopamine, noradrenaline and acetylcholine to distinct behavioural states, similar conclusions have not been as readily available for serotonin. Fascinatingly, despite clear links between serotonergic function and cognitive capacities as diverse as reward processing, exploration, and the psychedelic experience, over 95% of the serotonin in the body is released in the gastrointestinal tract, where it controls digestive muscle contractions (peristalsis). Here, we argue that framing neural serotonin as a rostral extension of the gastrointestinal serotonergic system dissolves much of the mystery associated with the central serotonergic system. Specifically, we outline that central serotonin activity mimics the effects of a digestion/satiety circuit mediated by hypothalamic control over descending serotonergic nuclei in the brainstem. We review commonalities and differences between these two circuits, with a focus on the heterogeneous expression of different classes of serotonin receptors in the brain. Much in the way that serotonin-induced peristalsis facilitates the work of digestion, serotonergic influences over cognition can be reframed as performing the work of cognition. Extending this analogy, we argue that the central serotonergic system allows the brain to arbitrate between different cognitive modes as a function of serotonergic tone: low activity facilitates cognitive automaticity, whereas higher activity helps to identify flexible solutions to problems, particularly if and when the initial responses fail. This perspective sheds light on otherwise disparate capacities mediated by serotonin, and also helps to understand why there are such pervasive links between serotonergic pathology and the symptoms of psychiatric disorders.
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Affiliation(s)
| | | | - Ishan C Walpola
- Prince of Wales Hospital , Randwick, New South Wales , Australia
| | | | | | - Jaan Aru
- University of Tartu , Tartu , Estonia
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Chronic rapid eye movement sleep restriction during juvenility has long-term effects on anxiety-like behaviour and neurotransmission of male Wistar rats. Pharmacol Biochem Behav 2022; 217:173410. [PMID: 35662652 DOI: 10.1016/j.pbb.2022.173410] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/24/2022] [Revised: 05/30/2022] [Accepted: 05/31/2022] [Indexed: 11/21/2022]
Abstract
Modernity imposes a toll on the sleep time of young population, with concomitant increase in symptoms of anxiety and depression. Whether there is a causal relationship between these events are only now being experimentally tested in humans and rodents. In a previous study, we showed that chronic sleep deprivation in juvenile-adolescent male rats led to increased anxiety-like behaviour and changes in noradrenaline and serotonin in the amygdala and hippocampus. In the present study we investigated whether early chronic sleep restriction affects emotional behaviour, stress response and neurochemistry in adulthood. From 21 to 42 days of age, Wistar male rats were submitted to sleep restriction by the multiple platform method or allowed to sleep freely. Forty-five days after this period, rats were tested in the elevated plus maze (EPM) and blood samples were collected from non-tested rats or 30 and 60 min after the EPM for determination of plasma corticosterone levels. Levels of monoamines were determined in the frontal cortex, hippocampus, amygdala and hypothalamus 60 min after the EPM. Sleep restriction resulted in increased anxiety-like behaviour, decreased noradrenaline levels in the amygdala and dopamine levels in the ventral hippocampus. Anxiety index was positively correlated with increased serotonin metabolism in the frontal cortex and greater dopamine metabolism in the ventral hippocampus, and negatively correlated with dopamine levels in the ventral hippocampus. These results suggest that sleep restriction in juvenility and adolescence induces persistent changes in emotional behaviour in adult male rats and that levels of anxiety are correlated with increased serotonin and dopamine metabolism in specific brain areas.
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5-HT2A receptor dysregulation in a schizophrenia relevant mouse model of NMDA receptor hypofunction. Transl Psychiatry 2022; 12:168. [PMID: 35459266 PMCID: PMC9033804 DOI: 10.1038/s41398-022-01930-0] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/10/2021] [Revised: 03/22/2022] [Accepted: 04/08/2022] [Indexed: 11/30/2022] Open
Abstract
Blockade of N-methyl-D-aspartate receptors (NMDAR) is known to augment cortical serotonin 2A receptors (5-HT2ARs), which is implicated in psychosis. However, the pathways from NMDAR hypofunction to 5-HT2AR up-regulation are unclear. Here we addressed in mice whether genetic deletion of the indispensable NMDAR-subunit Grin1 principally in corticolimbic parvalbumin-positive fast-spiking interneurons, could up-regulate 5-HT2ARs leading to cortical hyper-excitability. First, in vivo local-field potential recording revealed that auditory cortex in Grin1 mutant mice became hyper-excitable upon exposure to acoustic click-train stimuli that release 5-HT in the cortex. This excitability increase was reproduced ex vivo where it consisted of an increased frequency of action potential (AP) firing in layer 2/3 pyramidal neurons of mutant auditory cortex. Application of the 5-HT2AR agonist TCB-2 produced similar results. The effect of click-trains was reversed by the 5-HT2AR antagonist M100907 both in vivo and ex vivo. Increase in AP frequency of pyramidal neurons was also reversed by application of Gαq protein inhibitor BIM-46187 and G protein-gated inwardly-rectifying K+ (GIRK) channel activator ML297. In fast-spiking interneurons, 5-HT2AR activation normally promotes GABA release, contributing to decreased excitability of postsynaptic pyramidal neurons, which was missing in the mutants. Moreover, unlike the controls, the GABAA receptor antagonist (+)-bicuculline had little effect on AP frequency of mutant pyramidal neurons, indicating a disinhibition state. These results suggest that the auditory-induced hyper-excitable state is conferred via GABA release deficits from Grin1-lacking interneurons leading to 5-HT2AR dysregulation and GIRK channel suppression in cortical pyramidal neurons, which could be involved in auditory psychosis.
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Miyagishi H, Tsuji M, Miyagawa K, Kurokawa K, Mochida-Saito A, Takahashi K, Kosuge Y, Ishige K, Takeda H. Possible role of transcriptional regulation of 5-HT 1A receptor in the midbrain on unadaptation to stress in mice. Brain Res 2022; 1783:147859. [PMID: 35245487 DOI: 10.1016/j.brainres.2022.147859] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/11/2021] [Revised: 02/04/2022] [Accepted: 02/28/2022] [Indexed: 11/17/2022]
Abstract
The ability to adapt to stress is an essential defensive function of a living body, and disturbance of this ability in the brain may contribute to the development of affective illness. Previously, we reported that mice exposed to unadaptable restraint stress show emotional abnormality. Moreover, this emotional abnormality was alleviated by chronic treatment with flesinoxan, a serotonin (5-HT)1A receptor agonist. 5-HT1A receptor expression is regulated by several transcription factors such as nuclear deformed epidermal autoregulatory factor (NUDR/Deaf-1) and five prime repressors under dual repression binding protein 1 (Freud-1). The present study was designed to investigate the expression levels of 5-HT1A receptor and its transcription factors in the midbrain and hippocampus of stress-adaptive and -unadaptive mice. Mice were exposed to 14 days of repeated adaptable (1 h/day) or repeated unadaptable (4 h/day) restraint stress, or were left in their home cage (non-stressed groups). In a western blot analysis, a significant increase in the expression levels of 5HT1A receptor protein were observed in the hippocampal membrane fraction in stress-adaptive mice. In contrast, the expression levels of 5-HT1A receptor protein in stress-unadaptive mice were significantly increased in both cytoplasmic and membrane fraction of the midbrain. Furthermore, real-time PCR analysis revealed that, in the midbrain of stress-unadaptive mice, the expression levels of 5-HT1A receptor mRNA and Freud-1 or NUDR mRNA were significantly increased and decreased, respectively. These results suggest that increased expression of 5-HT1A receptor due to decrease in the expression of Freud-1 and NUDR in the midbrain may play a pivotal role in the emotional abnormality of stress-unadaptive mice.
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Affiliation(s)
- Hiroko Miyagishi
- Department of Pharmacology, School of Pharmacy, International University of Health and Welfare, 2600-1 Kitakanemaru, Ohtawara, Tochigi 324-8501, Japan; Laboratory of Pharmacology, School of Pharmacy, Nihon University, 7-7-1 Narashinodai, Funabashi, Chiba 274-8555, Japan
| | - Minoru Tsuji
- Department of Pharmacology, School of Pharmacy, International University of Health and Welfare, 2600-1 Kitakanemaru, Ohtawara, Tochigi 324-8501, Japan.
| | - Kazuya Miyagawa
- Department of Pharmacology, School of Pharmacy, International University of Health and Welfare, 2600-1 Kitakanemaru, Ohtawara, Tochigi 324-8501, Japan
| | - Kazuhiro Kurokawa
- Department of Pharmacology, School of Pharmacy, International University of Health and Welfare, 2600-1 Kitakanemaru, Ohtawara, Tochigi 324-8501, Japan
| | - Atsumi Mochida-Saito
- Department of Pharmacology, School of Pharmacy, International University of Health and Welfare, 2600-1 Kitakanemaru, Ohtawara, Tochigi 324-8501, Japan
| | - Kohei Takahashi
- Department of Pharmacology, School of Pharmacy, International University of Health and Welfare, 2600-1 Kitakanemaru, Ohtawara, Tochigi 324-8501, Japan
| | - Yasuhiro Kosuge
- Laboratory of Pharmacology, School of Pharmacy, Nihon University, 7-7-1 Narashinodai, Funabashi, Chiba 274-8555, Japan
| | - Kumiko Ishige
- Laboratory of Pharmacology, School of Pharmacy, Nihon University, 7-7-1 Narashinodai, Funabashi, Chiba 274-8555, Japan
| | - Hiroshi Takeda
- Department of Pharmacology, School of Pharmacy, International University of Health and Welfare, 2600-1 Kitakanemaru, Ohtawara, Tochigi 324-8501, Japan
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Role of Stress-Related Dopamine Transmission in Building and Maintaining a Protective Cognitive Reserve. Brain Sci 2022; 12:brainsci12020246. [PMID: 35204009 PMCID: PMC8869980 DOI: 10.3390/brainsci12020246] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/25/2022] [Revised: 02/05/2022] [Accepted: 02/08/2022] [Indexed: 01/27/2023] Open
Abstract
This short review presents the hypothesis that stress-dependent dopamine (DA) transmission contributes to developing and maintaining the brain network supporting a cognitive reserve. Research has shown that people with a greater cognitive reserve are better able to avoid symptoms of degenerative brain changes. The paper will review evidence that: (1) successful adaptation to stressors involves development and stabilization of effective but flexible coping strategies; (2) this process requires dynamic reorganization of functional networks in the adult brain; (3) DA transmission is amongst the principal mediators of this process; (4) age- and disease-dependent cognitive impairment is associated with dysfunctional connectivity both between and within these same networks as well as with reduced DA transmission.
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Ghin F, Beste C, Stock AK. Neurobiological mechanisms of control in alcohol use disorder - moving towards mechanism-based non-invasive brain stimulation treatments. Neurosci Biobehav Rev 2021; 133:104508. [PMID: 34942268 DOI: 10.1016/j.neubiorev.2021.12.031] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/18/2020] [Revised: 12/14/2021] [Accepted: 12/19/2021] [Indexed: 12/13/2022]
Abstract
Alcohol use disorder (AUD) is characterized by excessive habitual drinking and loss of control over alcohol intake despite negative consequences. Both of these aspects foster uncontrolled drinking and high relapse rates in AUD patients. Yet, common interventions mostly focus on the phenomenological level, and prioritize the reduction of craving and withdrawal symptoms. Our review provides a mechanistic understanding of AUD and suggests alternative therapeutic approaches targeting the mechanisms underlying dysfunctional alcohol-related behaviours. Specifically, we explain how repeated drinking fosters the development of rigid drinking habits and is associated with diminished cognitive control. These behavioural and cognitive effects are then functionally related to the neurobiochemical effects of alcohol abuse. We further explain how alterations in fronto-striatal network activity may constitute the neurobiological correlates of these alcohol-related dysfunctions. Finally, we discuss limitations in current pharmacological AUD therapies and suggest non-invasive brain stimulation (like TMS and tDCS interventions) as a potential addition/alternative for modulating the activation of both cortical and subcortical areas to help re-establish the functional balance between controlled and automatic behaviour.
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Affiliation(s)
- Filippo Ghin
- Cognitive Neurophysiology, Department of Child and Adolescent Psychiatry, Faculty of Medicine, TU Dresden, Germany; University Neuropsychology Center, Faculty of Medicine, TU Dresden, Germany
| | - Christian Beste
- Cognitive Neurophysiology, Department of Child and Adolescent Psychiatry, Faculty of Medicine, TU Dresden, Germany; University Neuropsychology Center, Faculty of Medicine, TU Dresden, Germany
| | - Ann-Kathrin Stock
- Cognitive Neurophysiology, Department of Child and Adolescent Psychiatry, Faculty of Medicine, TU Dresden, Germany; University Neuropsychology Center, Faculty of Medicine, TU Dresden, Germany; Biopsychology, Faculty of Psychology, TU Dresden, Dresden, Germany.
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41
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Kudo H, Okuyama MW, Sakamoto KQ, Uchida K, Sato K. Serotonin-manipulated juvenile green sea turtles Chelonia mydas exhibit reduced fear-like behaviour. ENDANGER SPECIES RES 2021. [DOI: 10.3354/esr01153] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/23/2022] Open
Abstract
Animals display fear-like behaviours before escaping from predators. This response triggers both behavioural and physiological changes in multiple body systems, allowing animals to escape danger and ensure survival. Fear-like behaviour is modulated by the serotonergic system in the brain of vertebrates, which shapes social behaviour and cooperative behaviours. Using fluoxetine (FLX), a common pharmaceutical that alters the levels of serotonin in the brain, we aimed to clarify whether the same is true in solitary animals like green turtles Chelonia mydas. Green turtles exhibit individual differences in their response to risk. If fear-related behaviours are regulated by the serotonin system in turtles, the fear-like responses of individuals injected with FLX could change. We therefore assessed the effect of FLX injection on the behavioural responses to a fear stimulus in 9 wild juvenile green turtles in an aquarium setting. We inserted a hand net as a stimulus into the aquarium (within a designated inspection zone) to elicit a fear-like behaviour and measured the time that turtles spent in this zone. All turtles exhibited fear-like behaviour and fled from the stimulus prior to any injection treatment. Turtles with control injection (no FLX) also fled and avoided the inspection zone with the fear stimulus. FLX injection appeared to reduce the turtles’ fear of the stimulus: The total time turtles injected with FLX spent in the inspection zone was significantly longer than for turtles that received a control medium injection. Control turtles fled from the stimulus and were initially vigilant and avoided the area with the stimulus, but then moved throughout the aquarium, including the inspection zone. These data suggest that fear-like behaviour is modulated by the serotonin-mediated nerve system in juvenile green turtles.
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Affiliation(s)
- H Kudo
- Atmosphere and Ocean Research Institute, The University of Tokyo, Kashiwa, Chiba 277-8564, Japan
| | - MW Okuyama
- Faculty of Medicine, Oita University, Yufu 879-5593, Japan
| | - KQ Sakamoto
- Atmosphere and Ocean Research Institute, The University of Tokyo, Kashiwa, Chiba 277-8564, Japan
| | - K Uchida
- Oita environmental conservation forum, Nishishinchi, Oita, Oita 870-0901, Japan
| | - K Sato
- Atmosphere and Ocean Research Institute, The University of Tokyo, Kashiwa, Chiba 277-8564, Japan
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Hwang S, Chung U, Chang Y, Kim E, Suk JW, Meffert H, Kratochvil C, Leibenluft E, Blair J. Neural Responses to Fluoxetine in Youths with Disruptive Behavior and Trauma Exposure: A Pilot Study. J Child Adolesc Psychopharmacol 2021; 31:562-571. [PMID: 34076503 PMCID: PMC8575058 DOI: 10.1089/cap.2020.0174] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/21/2022]
Abstract
Objective: A preliminary investigation of the impact of a serotonergic agent (fluoxetine) on symptom profile and neural response in youths with disruptive behavior disorders (DBDs) and a history of trauma exposure. Methods: There were three participant groups: (i) Youths with DBDs and trauma exposure who received fluoxetine treatment for 8 weeks (n = 11); (ii) A matched group of youths with DBDs and trauma exposure who received routine regular follow-up in an outpatient clinic (n = 10); and (iii) Typically developing youths (n = 18). All participants conducted an expression processing functional magnetic resonance imaging task twice, 8 weeks apart: (pretreatment and post-treatment for youths with DBDs). Results: Youths with DBDs and trauma exposure who received fluoxetine treatment compared to the other two groups showed: (i) significant improvement in externalizing, oppositional defiant disorder, irritability, anxiety-depression, and trauma-related symptoms; (ii) as a function of fearful expression intensity, significantly decreased amygdala response and increased recruitment of regions implicated in top-down attention control (insula cortex, inferior parietal lobule, and postcentral gyrus) and emotional regulation (ventromedial prefrontal cortex [vmPFC]); and (iii) correlation between DBD/irritability symptom improvement and increased activation of top-down attention control areas (inferior parietal lobule, insula cortex, and postcentral gyrus) and an emotion regulation area (vmPFC). Conclusions: This study provides preliminary evidence that a serotonergic agent (fluoxetine) can reduce disruptive behavior and mood symptoms in youths with DBDs and trauma exposure and that this may be mediated by enhanced activation of top-down attention control and emotion regulation areas (inferior parietal lobule, insula cortex, and vmPFC).
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Affiliation(s)
- Soonjo Hwang
- Department of Psychiatry, University of Nebraska Medical Center, Omaha, Nebraska, USA.,Address correspondence to: Soonjo Hwang, MD, Department of Psychiatry, University of Nebraska Medical Center, 985578 Nebraska Medical Center, Omaha, NE 68198-5578, USA
| | - Unsun Chung
- Department of Psychiatry and Department of Radiology, Kyoungbook National University Hospital, Daegu, Republic of Korea
| | - Yongmin Chang
- Department of Psychiatry and Department of Radiology, Kyoungbook National University Hospital, Daegu, Republic of Korea
| | - Eunji Kim
- Department of Psychiatry and Department of Radiology, Kyoungbook National University Hospital, Daegu, Republic of Korea
| | - Ji-Woo Suk
- Department of Psychiatry, University of Nebraska Medical Center, Omaha, Nebraska, USA
| | | | | | - Ellen Leibenluft
- Emotion and Development Branch, National Institute of Mental Health, Bethesda, Maryland, USA
| | - James Blair
- Center for Neurobehavioral Research, Boys Town National Research Hospital, Boys Town, Nebraska, USA
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43
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Linh NT, Guntoro B, Hoang Qui N. Immunomodulatory, behavioral, and nutritional response of tryptophan application on poultry. Vet World 2021; 14:2244-2250. [PMID: 34566345 PMCID: PMC8448653 DOI: 10.14202/vetworld.2021.2244-2250] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/10/2021] [Accepted: 07/26/2021] [Indexed: 12/12/2022] Open
Abstract
Tryptophan is an essential amino acid for all animals that was discovered through casein hydrolysis. The use of tryptophan as feed additives has been attracting the attention of many nutritionists because it cannot be synthesized enough in an animal’s body. Tryptophan or precursor to the vitamin niacin in the diet is important, and its supplementation for poultry is determined to improve the amino acid balance and promote the poultry’s growth performance through enhancing appetite, feed efficiency, and protein synthesis. Moreover, poultry in different growth phases, breeding, and conditions require various amounts of tryptophan. In addition, supplemented tryptophan also improves the immune response or the immunomodulatory activity of poultry to various diseases through the kynurenine pathway, especially diseases in the bursa. Furthermore, tryptophan also has a strong relationship with lysine (the ideal tryptophan/lysine ratio) in improving growth performance. However, tryptophan deficiency could affect the behavioral responses (e.g. pecking behavior and poultry stress) because tryptophan serves as a precursor for the neurotransmitter serotonin and the pineal hormone melatonin in the diet. This paper tried to summarize all information about applying tryptophan in the diets and illustrate the roles of tryptophan in the poultry industry.
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Affiliation(s)
- Nguyen Thuy Linh
- Department of Animal Science and Veterinary Medicine, School of Agriculture and Aquaculture, Tra Vinh University, Tra Vinh City, Vietnam
| | - Budi Guntoro
- Department of Livestock Social Economics, Faculty of Animal Science, Universitas Gadjah Mada, Yogyakarta, Indonesia
| | - Nguyen Hoang Qui
- Department of Livestock Social Economics, Faculty of Animal Science, Universitas Gadjah Mada, Yogyakarta, Indonesia
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44
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Gobbo E, Zupan Šemrov M. Neuroendocrine and Cardiovascular Activation During Aggressive Reactivity in Dogs. Front Vet Sci 2021; 8:683858. [PMID: 34434983 PMCID: PMC8381274 DOI: 10.3389/fvets.2021.683858] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/22/2021] [Accepted: 07/14/2021] [Indexed: 11/20/2022] Open
Abstract
Our aim was to investigate cardiovascular activation by measuring changes in facial and body surface temperature using infrared thermography, and neuroendocrine activation using salivary cortisol (CORT) and serotonin concentration (SER) in dogs exhibiting aggressive reactivity in real time. Based on two factors, owner-reported past aggressive behaviors, and detailed behavioral observations collected during a Socially Acceptable Behavior test consisting of 16 subtests and, each individual was categorized as aggressive or non-aggressive. CORT and SER showed no difference in neuroendocrine activity between dogs, but aggressive dogs with higher levels of aggression were found to have lower SER. Aggressive dogs also had an increase in facial temperature from pre-test values. The discovery of a correlation between tail wagging and left tail wagging with aggression level and aggression-related behaviors in aggressive dogs is further evidence of the right hemisphere specialization for aggression previously reported in the literature. This study provides the first evidence that both cardiovascular and neuroendocrine systems are activated during an active act of aggression in dogs.
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Affiliation(s)
- Elena Gobbo
- Department of Animal Science, Biotechnical Faculty, University of Ljubljana, Domžale, Slovenia
| | - Manja Zupan Šemrov
- Department of Animal Science, Biotechnical Faculty, University of Ljubljana, Domžale, Slovenia
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45
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Antunes DF, Teles MC, Zuelling M, Friesen CN, Oliveira RF, Aubin‐Horth N, Taborsky B. Early social deprivation shapes neuronal programming of the social decision-making network in a cooperatively breeding fish. Mol Ecol 2021; 30:4118-4132. [PMID: 34133783 PMCID: PMC8457231 DOI: 10.1111/mec.16019] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/27/2021] [Revised: 06/04/2021] [Accepted: 06/11/2021] [Indexed: 01/10/2023]
Abstract
The early social environment an animal experiences may have pervasive effects on its behaviour. The social decision-making network (SDMN), consisting of interconnected brain nuclei from the forebrain and midbrain, is involved in the regulation of behaviours during social interactions. In species with advanced sociality such as cooperative breeders, offspring are exposed to a large number and a great diversity of social interactions every day of their early life. This diverse social environment may have life-long consequences on the development of several neurophysiological systems within the SDMN, although these effects are largely unknown. We studied these life-long effects in a cooperatively breeding fish, Neolamprologus pulcher, focusing on the expression of genes involved in the monoaminergic and stress response systems in the SDMN. N. pulcher fry were raised until an age of 2 months either with their parents, subordinate helpers and same-clutch siblings (+F), or with same-clutch siblings only (-F). Analysis of the expression of glucocorticoid receptor, mineralocorticoid receptor, corticotropin releasing factor, dopamine receptors 1 and 2, serotonin transporter and DNA methyltransferase 1 genes showed that early social experiences altered the neurogenomic profile of the preoptic area. Moreover, the dopamine receptor 1 gene was up-regulated in the preoptic area of -F fish compared to +F fish. -F fish also showed up-regulation of GR1 expression in the dorsal medial telencephalon (functional equivalent to the basolateral amygdala), and in the dorsolateral telencephalon (functional equivalent to the hippocampus). Our results suggest that early social environment has life-long effects on the development of several neurophysiological systems within the SDMN.
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Affiliation(s)
- Diogo F. Antunes
- Division of Behavioural EcologyInstitute of Ecology and EvolutionUniversity of BernHinterkappelenSwitzerland
| | - Magda C. Teles
- Instituto Gulbenkian de CiênciaOeirasPortugal
- ISPA‐Instituto UniversitárioLisbonPortugal
| | - Matthew Zuelling
- Division of Evolutionary EcologyInstitute of Ecology and EvolutionUniversity of BernHinterkappelenSwitzerland
| | - Caitlin N. Friesen
- Department of Integrative BiologyThe University of Texas at AustinAustinTXUSA
| | - Rui F. Oliveira
- Instituto Gulbenkian de CiênciaOeirasPortugal
- ISPA‐Instituto UniversitárioLisbonPortugal
- Champalimaud ResearchLisbonPortugal
| | - Nadia Aubin‐Horth
- Département de Biologie et Institut de Biologie Intégrative et des Systèmes (IBIS)Université LavalQuébecQCCanada
| | - Barbara Taborsky
- Division of Behavioural EcologyInstitute of Ecology and EvolutionUniversity of BernHinterkappelenSwitzerland
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46
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Yuan Y, Wang H, Chen Q, Xie C, Li H, Lin L, Tian L. Illness experience and coping styles of young and middle-aged patients with sudden sensorineural hearing loss: a qualitative study. BMC Health Serv Res 2021; 21:742. [PMID: 34315453 PMCID: PMC8314487 DOI: 10.1186/s12913-021-06763-z] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/13/2021] [Accepted: 07/16/2021] [Indexed: 11/10/2022] Open
Abstract
Background The incidence of Sudden Sensorineural Hearing Loss (SSNHL) is increasing and tends to occur at a young age. The patient’s disease experience during treatment is related to their physical and mental health. Effective coping styles such as proactively solving problems and asking for help will alleviate the patients’ psychological symptoms and improve their quality of life. Aims and objectives To explore the illness experience and coping styles of young and middle-aged patients with SSNHL (age: 18–64 years), clarify the relationship between the two, and understand the psychological state and needs of the patients. Methods The purposive and maximum difference sampling method was used to conduct semi-structured interviews with 23 young and middle-aged SSNHL patients. The interview data were analyzed by Colaizzi’s seven-step analysis. Results The illness experience of young and middle-aged SSNHL patients was complex, including symptoms during the onset of deafness and emotional experience before and after diagnosis. The coping styles of young and middle-aged SSNHL patients were active and diverse, including active acquisition of information, change in living habits, and seeking the care and attention of medical staff. Illness experience and coping style influence each other: good illness experience leads to active coping styles; active coping style results in good illness experience. Conclusions The illness experience of young and middle-aged SSNHL patients includes not only physical symptoms, but also changes in psychological and emotional reactions. Good illness experience can lead patients to adopt active coping style. Active and effective coping styles, such as positive acquisition of information, change in living habits and seeking care and help, can improve patients’ illness experience. Supplementary Information The online version contains supplementary material available at 10.1186/s12913-021-06763-z.
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Affiliation(s)
- Yang Yuan
- The First Affiliated Hospital of Soochow University/School of Nursing, Medical College of Soochow University, No. 188 Shizi Road, 215006, Suzhou, People's Republic of China.,School of Nursing, Medical College of Soochow University, 215006, Suzhou, China
| | - Hong Wang
- School of Nursing, Medical College of Soochow University, 215006, Suzhou, China.,Suzhou Kowloon Hospital, Shanghai Jiao Tong University School of Medicine, 215021, Suzhou, China
| | - Qiuyun Chen
- School of Nursing, Medical College of Soochow University, 215006, Suzhou, China
| | - Congyan Xie
- School of Nursing, Medical College of Soochow University, 215006, Suzhou, China
| | - Haixia Li
- Suzhou Kowloon Hospital, Shanghai Jiao Tong University School of Medicine, 215021, Suzhou, China
| | - Lu Lin
- The First Affiliated Hospital of Soochow University/School of Nursing, Medical College of Soochow University, No. 188 Shizi Road, 215006, Suzhou, People's Republic of China. .,School of Nursing, Medical College of Soochow University, 215006, Suzhou, China.
| | - Li Tian
- The First Affiliated Hospital of Soochow University/School of Nursing, Medical College of Soochow University, No. 188 Shizi Road, 215006, Suzhou, People's Republic of China. .,School of Nursing, Medical College of Soochow University, 215006, Suzhou, China.
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47
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Gavioli EC, Holanda VAD, Calo G, Ruzza C. Nociceptin/orphanin FQ receptor system blockade as an innovative strategy for increasing resilience to stress. Peptides 2021; 141:170548. [PMID: 33862163 DOI: 10.1016/j.peptides.2021.170548] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/02/2021] [Revised: 03/24/2021] [Accepted: 03/30/2021] [Indexed: 12/27/2022]
Abstract
The ability to successfully cope with stress is known as 'resilience', and resilient individuals are less prone to develop psychopathologies. Understanding the neurobiological mechanisms of resilience may be instrumental to improve current therapies and benefit high-risk subjects. This review summarizes the complex interplay that exists between physiological and pathological responses to stressful events and the nociceptin/orphanin FQ (N/OFQ) - N/OFQ receptor (NOP) system, including: the effects of stress in regulating N/OFQ release and NOP expression; the ability of the N/OFQ-NOP system to modulate the hypothalamic-pituitary-adrenal axis; behavioral studies; and evidence in humans correlating this peptidergic system with psychopathologies. Available findings support the view that N/OFQ signaling stimulates the hypothalamic-pituitary-adrenal axis, thus increasing stress circulating hormones and corticotropin-releasing factor signaling. Additionally, activation of the NOP receptor inhibits monoamine transmission, including 5-HT, and this may contribute to maladaptive outcomes of stress. Ultimately, the N/OFQ system seems to have an important role in stress vulnerability, and blockade of NOP signaling may provide an innovative strategy for the treatment of stress related psychopathologies.
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Affiliation(s)
- Elaine C Gavioli
- Department of Biophysics and Pharmacology, Federal University of Rio Grande do Norte, Natal, Brazil
| | - Victor A D Holanda
- Department of Biophysics and Pharmacology, Federal University of Rio Grande do Norte, Natal, Brazil
| | - Girolamo Calo
- Department of Pharmaceutical and Pharmacological Sciences, University of Padova, Italy
| | - Chiara Ruzza
- Department of Neuroscience and Rehabilitation, University of Ferrara, Ferrara, Italy; LTTA Laboratory for Advanced Therapies, Technopole of Ferrara, Ferrara, Italy.
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48
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Marrero MG, Dado-Senn B, Field SL, Yang G, Driver JP, Laporta J. Chronic heat stress delays immune system development and alters serotonin signaling in pre-weaned dairy calves. PLoS One 2021; 16:e0252474. [PMID: 34086766 PMCID: PMC8177632 DOI: 10.1371/journal.pone.0252474] [Citation(s) in RCA: 21] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/26/2020] [Accepted: 05/16/2021] [Indexed: 12/27/2022] Open
Abstract
Exposure to heat stress can alter the development and immune system function in dairy calves. Serotonin is an immunomodulatory biogenic amine that functions as a neurotransmitter and as a stress-response mediator. Our objectives were to characterize the patterns of serum serotonin concentrations and the pattern of serotonin-related genes expressed by immune cells of calves exposed to chronic heat stress or heat stress abatement during early life, and to explore whether these might relate to immune system development. Dairy calves were exposed to chronic heat stress (HS; n = 6) or heat stress abatement (cooling, CL; n = 6) across the prenatal (late gestation, last 46 d) and postnatal (from birth to weaning, 56 d) developmental windows. Blood samples were collected to harvest serum (weekly, from d 1 to 49), to isolate of circulating leukocyte mRNA (at 1, 21 and 42 d of age) and characterize immune cell populations by flow cytometry (at 21 and 47 d of age). Calves exposed to chronic heat stress pre- and postnatally had lower red blood cell counts and lower circulating serotonin, immunoglobulin G, and B-lymphocytes compared to CL calves. Circulating blood leukocyte mRNA expression of serotonin receptors -1A, -1F, -4 and -5 was greater, while heat shock protein 70 and immune-related genes (i.e., TBX21, TLR4, and TGFβ) were lower in HS relative to CL calves. Peripheral blood leukocytes from all calves secreted serotonin and interleukin-6 after in-vitro lipopolysaccharide stimulation. However, the HS calves produced more serotonin and less interleukin-6 than CL calves when activated in-vitro. Together, our data suggest that providing heat stress abatement to dairy calves across prenatal and postnatal developmental windows might modulate the serotonin synthesis pathway in ways that may benefit humoral immunity against microbial pathogens.
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Affiliation(s)
- Marcela G. Marrero
- Department of Animal Sciences, University of Florida, Gainesville, Florida, United States of America
| | - Bethany Dado-Senn
- Department of Animal and Dairy Sciences, University of Wisconsin, Madison, Wisconsin, United States of America
| | - Sena L. Field
- Department of Animal and Dairy Sciences, University of Wisconsin, Madison, Wisconsin, United States of America
| | - Guan Yang
- Department of Animal Sciences, University of Florida, Gainesville, Florida, United States of America
| | - John P. Driver
- Department of Animal Sciences, University of Florida, Gainesville, Florida, United States of America
| | - Jimena Laporta
- Department of Animal and Dairy Sciences, University of Wisconsin, Madison, Wisconsin, United States of America
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49
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Alfonso S, Gesto M, Sadoul B. Temperature increase and its effects on fish stress physiology in the context of global warming. JOURNAL OF FISH BIOLOGY 2021; 98:1496-1508. [PMID: 33111333 DOI: 10.1111/jfb.14599] [Citation(s) in RCA: 179] [Impact Index Per Article: 44.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/15/2020] [Revised: 10/14/2020] [Accepted: 10/27/2020] [Indexed: 05/07/2023]
Abstract
The capacity of fishes to cope with environmental variation is considered to be a main determinant of their fitness and is partly determined by their stress physiology. By 2100, global ocean temperature is expected to rise by 1-4°C, with potential consequences for stress physiology. Global warming is affecting animal populations worldwide through chronic temperature increases and an increase in the frequency of extreme heatwave events. As ectotherms, fishes are expected to be particularly vulnerable to global warming. Although little information is available about the effects of global warming on stress physiology in nature, multiple studies describe the consequences of temperature increases on stress physiology in controlled laboratory conditions, providing insight into what can be expected in the wild. Chronic temperature increase constitutes a physiological load that can alter the ability of fishes to cope with additional stressors, which might compromise their fitness. In addition, rapid temperature increases are known to induce acute stress responses in fishes and might be of ecological relevance in particular situations. This review summarizes knowledge about effects of temperature increases on the stress physiology of fishes and discusses these in the context of global warming.
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Affiliation(s)
- Sébastien Alfonso
- COISPA Tecnologia & Ricerca, Stazione Sperimentale per lo Studio delle Risorse del Mare, Bari, Italy
| | - Manuel Gesto
- Section for Aquaculture, DTU Aqua, Technical University of Denmark, Hirtshals, Denmark
| | - Bastien Sadoul
- MARBEC, Ifremer, IRD, UM2, CNRS, Sète, France
- ESE, Ecology and Ecosystem Health, Institut Agro, INRAE, Rennes Cedex, France
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50
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Stettler PR, F Antunes D, Taborsky B. The serotonin 1A receptor modulates the social behaviour within groups of a cooperatively-breeding cichlid. Horm Behav 2021; 129:104918. [PMID: 33428923 DOI: 10.1016/j.yhbeh.2020.104918] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/23/2020] [Revised: 11/06/2020] [Accepted: 12/23/2020] [Indexed: 11/24/2022]
Abstract
The neurotransmitter serotonin (5-HT) reduces aggressive behaviour in a number of vertebrates, and the 5-HT1A receptor is known to be involved in this regulation. However, the role of this receptor in the modulation of sociopositive behaviour remains largely unknown. Here we investigated the role of the 5-HT1A receptor in the regulation of aggressive, submissive and affiliative behaviour in the cooperatively-breeding cichlid Neolamprologus pulcher. In two experiments, we performed intramuscular injections of a 5-HT1A agonist (8-OH-DPAT) and antagonist (Way-100635) followed by recordings of social behaviour of injected fish within their social groups. We determined the concentrations and post-injection times when the drugs had the greatest effect on social behaviour. We recorded spontaneous social behaviour in both experiments. In the second experiment we also recorded behaviour after social groups received a territorial challenge by live presentations of either conspecifics or egg predators. The 5-HT1A agonist caused an increase in aggression and a decrease in submission and affiliation, whereas the antagonist had the opposite effects. Thus, the 5-HT1A receptor plays an important regulatory role not only for aggressive but also sociopositive behaviour.
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Affiliation(s)
- Pia R Stettler
- Division of Behavioural Ecology, Institute of Ecology and Evolution, University of Bern, Wohlenstrasse 50A, 3032 Hinterkappelen, Switzerland.
| | - Diogo F Antunes
- Division of Behavioural Ecology, Institute of Ecology and Evolution, University of Bern, Wohlenstrasse 50A, 3032 Hinterkappelen, Switzerland.
| | - Barbara Taborsky
- Division of Behavioural Ecology, Institute of Ecology and Evolution, University of Bern, Wohlenstrasse 50A, 3032 Hinterkappelen, Switzerland.
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