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Peng K, Li J, You S, Xu Y, Qin L, Bao W, Tan L, Zhang X. Oxytocin in periaqueductal gray plasticly regulates strain-dependent social recognition memory in mice, modeling social identity. Commun Biol 2025; 8:881. [PMID: 40481136 PMCID: PMC12144289 DOI: 10.1038/s42003-025-08307-1] [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: 08/23/2024] [Accepted: 05/27/2025] [Indexed: 06/11/2025] Open
Abstract
Social identity differences are crucial for gregarious animals, impacting survival and social development. This is particularly evident in humans, where social stratification, cultural divides, and ethnic differences influence societal dynamics. Social recognition memory plays a central role in this process, maintaining social order by allowing individuals to distinguish familiar members within their group. Notably, social recognition memory exhibits differences: within a group, individuals form detailed memories of each member (individualized memory), while for out-group members, a more generalized memory of the entire group forms (categorized memory). Although this phenomenon has been explored in human studies, current research techniques and methods have limited investigations into the underlying neural mechanisms, especially their plasticity and regulatory mechanisms. This study utilizes mice to establish an experimental model for investigating differences in social recognition memory and its neural basis. We demonstrate that mice also exhibit social identity-driven memory recognition patterns. Mice form individualized memories for same-strain individuals but categorized memories for different strains, and the type of social recognition memory could be regulated by oxytocin level of ventrolateral periaqueductal gray. These findings demonstrate that oxytocin and its receptors in the ventrolateral periaqueductal gray are essential for constructing and plastically regulating intergroup social memory in mice.
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Affiliation(s)
- Kaizhen Peng
- School of Basic Medicine, Kunming Medical University, Kunming, China
| | - Jie Li
- School of Basic Medicine, Kunming Medical University, Kunming, China
| | - Shiyu You
- School of Basic Medicine, Kunming Medical University, Kunming, China
| | - Yuanyuan Xu
- School of Basic Medicine, Kunming Medical University, Kunming, China
| | - Liuting Qin
- School of Basic Medicine, Kunming Medical University, Kunming, China
| | - Weiyan Bao
- School of Basic Medicine, Kunming Medical University, Kunming, China
| | - Lili Tan
- School of Government, Yunnan University, Kunming, China.
| | - Xiaomin Zhang
- School of Basic Medicine, Kunming Medical University, Kunming, China.
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Zhang B, Chen J, Wang J, Pan X. Arsenic exposure induces neural cells senescence and abnormal lipid droplet accumulation leading to social memory impairment in mice. ENVIRONMENTAL POLLUTION (BARKING, ESSEX : 1987) 2025; 368:125779. [PMID: 39894154 DOI: 10.1016/j.envpol.2025.125779] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/29/2024] [Revised: 01/08/2025] [Accepted: 01/30/2025] [Indexed: 02/04/2025]
Abstract
The long-term harmful effects of arsenic exposure remain one of the important public health issues. The effects of arsenic exposure on the central nervous system, particularly concerning brain structure and function, have been garnering increasing attention. Hence, the aim of this study was to investigate the impact of chronic low-dose arsenic exposure on murine social memory and to elucidate the underlying molecular mechanisms. Male C57BL/6 mice at six months of age were randomly assigned to a control group and three treatment groups with different arsenic concentrations (50, 100, and 200 μg/L), with exposure durations of 30, 90, 180, and 360 days. The five-social memory test and three-chamber social memory test results indicated that chronic low-dose arsenic exposure disrupted social memory in mice. Further analysis revealed that arsenic exposure led to degeneration of neurons within the dorsal CA2 of the hippocampus (dCA2) and the lateral entorhinal cortex (LEC), which are pivotal for the modulation of social memory, and dCA2 neurons demonstrated structural disruptions and cytoplasmic fragmentation. In addition, arsenic exposure induced neurons and glial cells senescence in both dCA2 and LEC, with a particularly pronounced effect in microglia, and worse with dosage increasing of arsenic exposure, correlating with elevated expression levels of p16INK4A, ferritin light chain and the senescence-associated secretory factors TNF-α and IL-1β, and reduced expression of Lamin B1. Moreover, arsenic exposure triggered substantial cytoplasmic lipid droplets accumulation in neurons, astrocytes and microglia, with an upregulation of PLIN2 expression, a protein associated with lipid droplet formation in astrocytes. At the same time, the aberrant accumulation of lipid droplets further aggravated the astrocytes and microglia aging, especially microglia. Additionally, correlation analysis revealed that social memory impairment was negatively correlated with nerve cell senescence and lipid accumulation. Our findings suggest that arsenic exposure induced cellular functional abnormalities by triggering cellular senescence and the accumulation of lipid droplets, thereby exacerbated neuronal degeneration and result in impaired social memory in mice.
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Affiliation(s)
- Bo Zhang
- The Key Laboratory of Environmental Pollution Monitoring and Disease Control, Ministry of Education, School of Public Health, Guizhou Medical University, Guiyang, 561113, China; Collaborative Innovation Center for Prevention and Control of Endemic and Ethnic Regional Diseases Co-constructed By the Province and Ministry, Guizhou Medical University, Guiyang, 561113, China.
| | - Junhong Chen
- The Key Laboratory of Environmental Pollution Monitoring and Disease Control, Ministry of Education, School of Public Health, Guizhou Medical University, Guiyang, 561113, China
| | - Jiaojiao Wang
- The Key Laboratory of Environmental Pollution Monitoring and Disease Control, Ministry of Education, School of Public Health, Guizhou Medical University, Guiyang, 561113, China
| | - Xueli Pan
- The Key Laboratory of Environmental Pollution Monitoring and Disease Control, Ministry of Education, School of Public Health, Guizhou Medical University, Guiyang, 561113, China.
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Blasi E, Di Cesare B, Pisaneschi A, Campolongo P, Morena M. Social buffering during fear extinction rescues long-term trauma-induced memory and emotional behavioral alterations in rats. Transl Psychiatry 2025; 15:64. [PMID: 39984453 PMCID: PMC11845759 DOI: 10.1038/s41398-025-03285-8] [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: 02/15/2024] [Revised: 01/14/2025] [Accepted: 02/12/2025] [Indexed: 02/23/2025] Open
Abstract
Post-Traumatic Stress Disorder (PTSD) is a psychiatric disease that may develop after experiencing a traumatic event and it is characterized by resistance to extinction of the traumatic memory. Psychotherapy, which mainly focuses on favoring fear memory extinction, represents the first-line treatment for PTSD. However, this approach is not always successful. Emerging evidence suggests the importance of a social support in alleviating PTSD symptomatology; however, the efficacy of group therapy for PTSD remains controversial. Here, we evaluated the impact of social support on the efficacy of fear extinction sessions in a chronic PTSD-like rat model. We tested the hypothesis that the presence of a social partner during temporally spaced extinction sessions (to mimic the presence of a social support during therapy) or after the extinction sessions in a neutral environment (to mimic the presence of a social support outside of the therapy setting) would ameliorate long-term PTSD-like symptomatology. Extinction sessions were carried out under different conditions: (i) alone; (ii) with a social partner never exposed to the trauma; (iii) with a trauma-exposed partner. In a separate set of experiments, rats were exposed to the extinction sessions alone and, immediately thereafter, paired with a social partner, as indicated above, in a different context. Extinction sessions carried out in the presence of a social partner never exposed to the traumatic experience rescued long-term trauma-induced PTSD-like symptomatology. We provide evidence of beneficial effects of a "healthy" social support during extinction sessions in ameliorating both immediate and persistent over time cognitive and emotional PTSD-like symptoms.
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Affiliation(s)
- Eleonora Blasi
- Department of Physiology and Pharmacology, Sapienza University of Rome, Rome, Italy
- Neuropharmacology Unit, European Center for Brain Research (CERC), Santa Lucia Foundation IRCCS, Rome, Italy
| | - Benedetta Di Cesare
- Department of Physiology and Pharmacology, Sapienza University of Rome, Rome, Italy
- Neuropharmacology Unit, European Center for Brain Research (CERC), Santa Lucia Foundation IRCCS, Rome, Italy
| | - Arianna Pisaneschi
- Department of Physiology and Pharmacology, Sapienza University of Rome, Rome, Italy
- Neuropharmacology Unit, European Center for Brain Research (CERC), Santa Lucia Foundation IRCCS, Rome, Italy
| | - Patrizia Campolongo
- Department of Physiology and Pharmacology, Sapienza University of Rome, Rome, Italy
- Neuropharmacology Unit, European Center for Brain Research (CERC), Santa Lucia Foundation IRCCS, Rome, Italy
| | - Maria Morena
- Department of Physiology and Pharmacology, Sapienza University of Rome, Rome, Italy.
- Neuropharmacology Unit, European Center for Brain Research (CERC), Santa Lucia Foundation IRCCS, Rome, Italy.
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Zhou Y, Yuan X, Guo M. Unlocking NAC's potential ATF4 and m6A dynamics in rescuing cognitive impairments in PTSD. Metab Brain Dis 2025; 40:129. [PMID: 39954094 DOI: 10.1007/s11011-024-01485-7] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/21/2023] [Accepted: 11/21/2024] [Indexed: 02/17/2025]
Abstract
In this study, we investigated the therapeutic potential of N-acetylcysteine (NAC) in a mouse model of post-traumatic stress disorder (PTSD) induced by a single prolonged stress (SPS) protocol. Our findings demonstrate that NAC treatment significantly improved cognitive function and mitigated hippocampal neuronal apoptosis in PTSD model mice. These positive effects were accompanied by a reduction in m6A methylation levels and activating transcription factor 4 (ATF4) expression. Silencing ATF4 further attenuated hippocampal neuronal apoptosis and cognitive dysfunction, while ATF4 overexpression partially reversed the beneficial effects of NAC. It suggests that NAC's efficacy in PTSD may be mediated by its regulation of ATF4 expression and m6A methylation levels. Overall, our study provides valuable insights into the potential mechanism of action for NAC in PTSD treatment, offering promising avenues for future therapeutic strategies.
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Affiliation(s)
- Yanling Zhou
- The Fourth People's Hospital of Haikou, Haikou, 570311, P. R. China
| | - Xiuhong Yuan
- Haikou People's Hospital, Haikou Affiliated Hospital of Central South University Xiangya School of Medicine, Haikou, 570208, P. R. China
- Department of Clinical Psychology, The Third Xiangya Hospital of Central South University, Changsha, 410013, P. R. China
| | - Min Guo
- Hainan General Hospital, No.19, Xiuhua Road, Xiuying District, Haikou, 570311, Hainan Province, P. R. China.
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Lin B, Jin Z, Park G, Ge Q, Singh K, Ryan V WG, Imami AS, Naghavi F, Miller OA, Khan S, Lu H, McCullumsmith RE, Du J. Mice lacking acid-sensing ion channel 2 in the medial prefrontal cortex exhibit social dominance. SCIENCE ADVANCES 2024; 10:eadn7573. [PMID: 39453995 PMCID: PMC11506137 DOI: 10.1126/sciadv.adn7573] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/27/2023] [Accepted: 09/23/2024] [Indexed: 10/27/2024]
Abstract
Social dominance is essential for maintaining a stable society and has both positive and negative impacts on social animals, including humans. However, the regulatory mechanisms governing social dominance, as well as the crucial regulators and biomarkers involved, remain poorly understood. We discover that mice lacking acid-sensing ion channel 2 (ASIC2) exhibit persistently higher social dominance than their wild-type cagemates. Conversely, overexpression of ASIC2 in the medial prefrontal cortex reverses the dominance hierarchy observed in ASIC2 knockout (Asic2-/-) mice. Asic2-/- neurons exhibit increased synaptic transmission and plasticity, potentially mediated by protein kinase A signaling pathway. Furthermore, ASIC2 plays distinct functional roles in excitatory and inhibitory neurons, thereby modulating the balance of neuronal activities underlying social dominance behaviors-a phenomenon suggestive of a cell subtype-specific mechanism. This research lays the groundwork for understanding the mechanisms of social dominance, offering potential insights for managing social disorders, such as depression and anxiety.
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Affiliation(s)
- Boren Lin
- Department of Anatomy and Neurobiology, University of Tennessee Health Science Center, Memphis, TN 38163, USA
- Department of Biological Sciences, University of Toledo, Toledo, OH 43606, USA
| | - Zhen Jin
- Department of Anatomy and Neurobiology, University of Tennessee Health Science Center, Memphis, TN 38163, USA
| | - Gyeongah Park
- Department of Anatomy and Neurobiology, University of Tennessee Health Science Center, Memphis, TN 38163, USA
| | - Qian Ge
- Department of Anatomy and Neurobiology, University of Tennessee Health Science Center, Memphis, TN 38163, USA
| | - Kritika Singh
- Department of Biological Sciences, University of Toledo, Toledo, OH 43606, USA
| | - William G. Ryan V
- Department of Neuroscience, University of Toledo, Toledo, OH 43606, USA
| | - Ali Sajid Imami
- Department of Neuroscience, University of Toledo, Toledo, OH 43606, USA
| | - Farzaneh Naghavi
- Department of Neuroscience, University of Toledo, Toledo, OH 43606, USA
| | - Olivia Ann Miller
- Department of Biological Sciences, University of Toledo, Toledo, OH 43606, USA
| | - Saira Khan
- Department of Biological Sciences, University of Toledo, Toledo, OH 43606, USA
| | - Hui Lu
- Department of Pharmacology and Physiology, George Washington University School of Medicine, Washington, DC 20037, USA
| | - Robert E. McCullumsmith
- Department of Neuroscience, University of Toledo, Toledo, OH 43606, USA
- Neurosciences Institute, ProMedica, Toledo, OH 43614, USA
| | - Jianyang Du
- Department of Anatomy and Neurobiology, University of Tennessee Health Science Center, Memphis, TN 38163, USA
- Neuroscience Institute, University of Tennessee Health Science Center, Memphis, TN 38163, USA
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Löffler-Stastka H. Clinical, scientific and stakeholders’ caring about identity perturbations. World J Psychiatry 2024; 14:1422-1428. [DOI: 10.5498/wjp.v14.i10.1422] [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: 05/23/2024] [Revised: 08/13/2024] [Accepted: 09/23/2024] [Indexed: 10/17/2024] Open
Abstract
In this editorial we comment on the article by Zhang et al published in the recent issue of the World Journal of Psychiatry. We focus on identity diffusion, identity perturbations, their origin and developmental pathways. This is an upcoming problem in the society as not only school children are affected. Adolescents and young people suffer from uncertainty in gender identity, in self-image, migration effects due to chronic crises caused by war, pandemic disruptions or climate change. We show how such chronic uncertainty can be cared for, treated, and contained. The key is affective holding, reflection and to provide adequate affective mentalizing in a close concomitant way. These key features also depend on ambient conditions, such as psychotherapeutic care. In a qualitative interview study carried out in a cyclical research design with a comparative analysis on the basis of thematic coding using Grounded Theory Methodology we found institutionalized defenses in health policies. Professionals request better training and adequat academic knowledge as well as research into unresolved areas for improvement of the ambient conditions for adequat development of the self. Practice points for further clinical and scientific development are given and discussed.
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Huang XY, Xue LL, Ma RF, Shi JS, Wang TH, Xiong LL, Yu CY. Inhibition of CXCR4: A perspective on miracle fruit seed for Alzheimer's disease treatment. Exp Neurol 2024; 379:114841. [PMID: 38821198 DOI: 10.1016/j.expneurol.2024.114841] [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: 01/23/2024] [Revised: 04/06/2024] [Accepted: 05/27/2024] [Indexed: 06/02/2024]
Abstract
Alzheimer's disease (AD) is the most prevalent type of dementia, and its causes are currently diverse and not fully understood. In a previous study, we discovered that short-term treatment with miracle fruit seed (MFS) had a therapeutic effect on AD model mice, however, the precise mechanism behind the effect remains unclear. In this research, we aimed to establish the efficacy and safety of long-term use of MFS in AD model mice. A variety of cytokines and chemokines have been implicated in the development of AD. Previous studies have validated a correlation between the expression levels of C-X-C chemokine receptor type 4 (CXCR4) and disease severity in AD. In this research, we observed an upregulation of CXCR4 expression in hippocampal tissues in the AD model group, which was then reversed after MFS treatment. Moreover, CXCR4 knockout led to improving cognitive function in AD model mice, and MFS showed the ability to regulate CXCR4 expression. Finally, our findings indicate that CXCR4 knockout and long-term MFS treatment produce comparable effects in treating AD model mice. In conclusion, this research demonstrates that therapeutic efficacy and safety of long-term use of MFS in AD model mice. MFS treatment and the subsequent reduction of CXCR4 expression exhibit a neuroprotective role in the brain, highlighting their potential as therapeutic targets for AD.
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Affiliation(s)
- Xue-Yan Huang
- Department of Neurology, Affiliated Hospital of Zunyi Medical University, Zunyi, Guizhou, China
| | - Lu-Lu Xue
- State Key Laboratory of Biotherapy, Sichuan University, Chengdu, Sichuan, China
| | - Rui-Fang Ma
- School of Basic Medical Sciences, Kunming Medical University, Kunming, Yunnan, China
| | - Jing-Shan Shi
- Key Laboratory of Basic Pharmacology of Ministry of Education and Joint International Research Lab of Ethnomedicine of Ministry of Education, Zunyi Medical University, Zunyi, Guizhou, China
| | - Ting-Hua Wang
- Department of Neurology, Affiliated Hospital of Zunyi Medical University, Zunyi, Guizhou, China.
| | - Liu-Lin Xiong
- Department of Anesthesiology, Affiliated Hospital of Zunyi Medical University, Zunyi, Guizhou, China.
| | - Chang-Yin Yu
- Department of Neurology, Affiliated Hospital of Zunyi Medical University, Zunyi, Guizhou, China.
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Ruge J, Ehlers MR, Kastrinogiannis A, Klingelhöfer-Jens M, Koppold A, Abend R, Lonsdorf TB. How adverse childhood experiences get under the skin: A systematic review, integration and methodological discussion on threat and reward learning mechanisms. eLife 2024; 13:e92700. [PMID: 39012794 PMCID: PMC11251725 DOI: 10.7554/elife.92700] [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: 10/26/2023] [Accepted: 06/26/2024] [Indexed: 07/18/2024] Open
Abstract
Adverse childhood experiences (ACEs) are a major risk factor for the development of multiple psychopathological conditions, but the mechanisms underlying this link are poorly understood. Associative learning encompasses key mechanisms through which individuals learn to link important environmental inputs to emotional and behavioral responses. ACEs may impact the normative maturation of associative learning processes, resulting in their enduring maladaptive expression manifesting in psychopathology. In this review, we lay out a systematic and methodological overview and integration of the available evidence of the proposed association between ACEs and threat and reward learning processes. We summarize results from a systematic literature search (following PRISMA guidelines) which yielded a total of 81 articles (threat: n=38, reward: n=43). Across the threat and reward learning fields, behaviorally, we observed a converging pattern of aberrant learning in individuals with a history of ACEs, independent of other sample characteristics, specific ACE types, and outcome measures. Specifically, blunted threat learning was reflected in reduced discrimination between threat and safety cues, primarily driven by diminished responding to conditioned threat cues. Furthermore, attenuated reward learning manifested in reduced accuracy and learning rate in tasks involving acquisition of reward contingencies. Importantly, this pattern emerged despite substantial heterogeneity in ACE assessment and operationalization across both fields. We conclude that blunted threat and reward learning may represent a mechanistic route by which ACEs may become physiologically and neurobiologically embedded and ultimately confer greater risk for psychopathology. In closing, we discuss potentially fruitful future directions for the research field, including methodological and ACE assessment considerations.
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Affiliation(s)
- Julia Ruge
- University Medical Center Hamburg-Eppendorf, Institute for Systems NeuroscienceHamburgGermany
| | | | - Alexandros Kastrinogiannis
- University Medical Center Hamburg-Eppendorf, Institute for Systems NeuroscienceHamburgGermany
- Department of Neurology, Max Planck Institute for Human Cognitive and Brain SciencesLeipzigGermany
| | - Maren Klingelhöfer-Jens
- University Medical Center Hamburg-Eppendorf, Institute for Systems NeuroscienceHamburgGermany
- University of BielefeldBielefeldGermany
| | - Alina Koppold
- University Medical Center Hamburg-Eppendorf, Institute for Systems NeuroscienceHamburgGermany
| | | | - Tina B Lonsdorf
- University Medical Center Hamburg-Eppendorf, Institute for Systems NeuroscienceHamburgGermany
- University of BielefeldBielefeldGermany
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Dubey S, Ghosh R, Dubey MJ, Chatterjee S, Das S, Benito-León J. Redefining Cognitive Domains in the Era of ChatGPT: A Comprehensive Analysis of Artificial Intelligence's Influence and Future Implications. MEDICAL RESEARCH ARCHIVES 2024; 12:5383. [PMID: 39469137 PMCID: PMC11515803 DOI: 10.18103/mra.v12i6.5383] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Indexed: 10/30/2024]
Abstract
Background and Objectives Despite its extensive utilization, research on Chat Generative Pre-trained Transformer (ChatGPT)'s potential negative impact on specific cognitive processes is scarce. This article explores the widespread use of ChatGPT in educational, corporate, and various other sectors, focusing on its interaction with distinct cognitive domains such as attention, executive function, language, memory, visuospatial abilities, and social cognition. Methods A literature review was conducted using PubMed, identifying 256 articles, with 29 peer-reviewed articles analyzed after screening for relevance. Results The review emphasizes the extraordinary capabilities of the human brain, which often go unrecognized, and argues for the importance of maintaining and enhancing natural cognitive abilities using artificial intelligence tools like ChatGPT as an aid rather than a replacement. The findings highlight the advanced reasoning capabilities of ChatGPT, blending intuitive and deliberate cognitive processes. Conclusion Building a socio-cognitive architecture for collective human-machine intelligence has significant potential. While ChatGPT offers impressive capabilities, over-reliance on it for cognitive tasks can lead to the erosion of essential skills. It is crucial to find a balance between leveraging artificial intelligence's advantages and preserving our natural cognitive abilities, ensuring continuous practice and engagement in traditional cognitive exercises.
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Affiliation(s)
- Souvik Dubey
- Department of Neuromedicine, Bangur Institute of Neurology (BIN) Kolkata, West Bengal, India
| | - Ritwik Ghosh
- Department of General Medicine, Burdwan Medical College, and Hospital, Burdwan, West Bengal, India
| | - Mahua Jana Dubey
- Department of Psychiatry, Berhampore Mental Hospital, Berhampore, West Bengal, India
| | - Subhankar Chatterjee
- Department of Endocrinology and Metabolism, Medical College Kolkata, Kolkata, West Bengal, India
| | - Shambaditya Das
- Department of Neuromedicine, Bangur Institute of Neurology (BIN) Kolkata, West Bengal, India
| | - Julián Benito-León
- Department of Neurology, University Hospital “12 de Octubre”, Madrid, Spain
- Instituto de Investigación Sanitaria Hospital 12 de Octubre (imas12), Madrid, Spain
- Centro de Investigación Biomédica en Red Sobre Enfermedades Neurodegenerativas (CIBERNED), Madrid, Spain
- Department of Medicine, Faculty of Medicine, Complutense University, Madrid, Spain
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King C, Mali I, Strating H, Fangman E, Neyhard J, Payne M, Bossmann SH, Plakke B. Region-Specific Brain Volume Changes Emerge in Adolescence in the Valproic Acid Model of Autism and Parallel Human Findings. Dev Neurosci 2024; 47:68-80. [PMID: 38679020 PMCID: PMC11511791 DOI: 10.1159/000538932] [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: 01/11/2024] [Accepted: 04/09/2024] [Indexed: 05/01/2024] Open
Abstract
INTRODUCTION Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by social and communication deficits, cognitive dysfunction, and stereotyped repetitive behaviors. Regional volume changes are commonly observed in individuals with ASD. To examine volumetric dysregulation across adolescence, the valproic acid (VPA) model was used to induce ASD-like phenotypes in rats. METHOD Regional volumes were obtained via magnetic resonance imaging at either postnatal day 28 or postnatal day 40 (P40), which correspond to early and late adolescence, respectively. RESULTS Consistent with prior research, VPA animals had reduced total brain volume compared to control animals. A novel outcome was that VPA animals had overgrown right hippocampi at P40. Differences in the pattern of development of the anterior cingulate cortex were also observed in VPA animals. Differences for the posterior cingulate were only observed in males, but not females. CONCLUSION These results demonstrate differences in region-specific developmental trajectories between control and VPA animals and suggest that the VPA model may capture regional volume changes consistent with human ASD. INTRODUCTION Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by social and communication deficits, cognitive dysfunction, and stereotyped repetitive behaviors. Regional volume changes are commonly observed in individuals with ASD. To examine volumetric dysregulation across adolescence, the valproic acid (VPA) model was used to induce ASD-like phenotypes in rats. METHOD Regional volumes were obtained via magnetic resonance imaging at either postnatal day 28 or postnatal day 40 (P40), which correspond to early and late adolescence, respectively. RESULTS Consistent with prior research, VPA animals had reduced total brain volume compared to control animals. A novel outcome was that VPA animals had overgrown right hippocampi at P40. Differences in the pattern of development of the anterior cingulate cortex were also observed in VPA animals. Differences for the posterior cingulate were only observed in males, but not females. CONCLUSION These results demonstrate differences in region-specific developmental trajectories between control and VPA animals and suggest that the VPA model may capture regional volume changes consistent with human ASD.
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Affiliation(s)
- Cole King
- Psychological Sciences, Kansas State University, Manhattan, KS, USA
| | - Ivina Mali
- Department of Chemistry, Kansas State University, Manhattan, KS, USA
| | - Hunter Strating
- Psychological Sciences, Kansas State University, Manhattan, KS, USA
| | | | - Jenna Neyhard
- Psychological Sciences, Kansas State University, Manhattan, KS, USA
| | - Macy Payne
- Department of Chemistry, Kansas State University, Manhattan, KS, USA
| | | | - Bethany Plakke
- Psychological Sciences, Kansas State University, Manhattan, KS, USA
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Lv Y, Su H, Li R, Yang Z, Chen Q, Zhang D, Liang S, Hu C, Ni X. A cross-sectional study of the major risk factor at different levels of cognitive performance within Chinese-origin middle-aged and elderly individuals. J Affect Disord 2024; 349:377-383. [PMID: 38199420 DOI: 10.1016/j.jad.2024.01.069] [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: 06/12/2023] [Revised: 12/20/2023] [Accepted: 01/04/2024] [Indexed: 01/12/2024]
Abstract
OBJECTIVE Senior citizens suffering from cognitive impairment (CI) are on the East Asia rise. Multiple variables could lead to inter-/intra-individual cognition effectiveness variations, though previous research efforts did not consider weighting issues. METHODS This study scrutinized 5639 participants meeting required inclusion criteria by the CHARLS. Cognitive capacity was evaluated through Mini-Mental State Examination (MMSE). Considering that MMSE scorings were not following normal distribution, a non-parametric test and multiple linear regression were performed to screen candidate variables linked to cognitive capacity. Such applicability of candidate factors in the cumulative effect and the weighting of the impact on cognitive performance were evaluated by random forest (RF) algorithm. RESULTS Age, gender, education, marital status, residence, the type of residence, exercise, socialization level and drinking were correlated to MMSE scorings (p < 0.05). Among them, age, education, gender and sociality were correlated to individual MMSE items (p < 0.05). Regardless of MMSE scores and several MMSE items, age is always a prime factor. However, in the attention and computation item, education is better than age and ranks first. CONCLUSIONS This preliminary study prompted age, education, gender, and sociality with varying weightings to be linked to cognitive capacity within a Chinese cohort by differing cognitive aspects. At different levels of cognitive performance, the main risk factors are basically similar, but there are still some differences.
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Affiliation(s)
- Yuan Lv
- Jiangbin Hospital of Guangxi Zhuang Autonomous Region, 530021, PR China
| | - Huabin Su
- Jiangbin Hospital of Guangxi Zhuang Autonomous Region, 530021, PR China
| | - Rongqiao Li
- Jiangbin Hospital of Guangxi Zhuang Autonomous Region, 530021, PR China
| | - Ze Yang
- The Key Laboratory of Geriatrics, Beijing Institute of Geriatrics, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing Hospital/National Center of Gerontology of National Health Commission, 100730, PR China
| | - Qing Chen
- Jiangbin Hospital of Guangxi Zhuang Autonomous Region, 530021, PR China
| | - Di Zhang
- Jiangbin Hospital of Guangxi Zhuang Autonomous Region, 530021, PR China
| | - Shuolin Liang
- Jiangbin Hospital of Guangxi Zhuang Autonomous Region, 530021, PR China
| | - Caiyou Hu
- Jiangbin Hospital of Guangxi Zhuang Autonomous Region, 530021, PR China
| | - Xiaolin Ni
- Department of Biomedical Engineering, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100005, PR China.
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12
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Zhou S, Cui X, Chen J, Luo M, Ouyang W, Tong J, Xie Z, Le Y. Single exposure to anesthesia/surgery in neonatal mice induces cognitive impairment in young adult mice. Free Radic Biol Med 2024; 214:184-192. [PMID: 38369077 DOI: 10.1016/j.freeradbiomed.2024.02.017] [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: 01/01/2024] [Revised: 01/31/2024] [Accepted: 02/15/2024] [Indexed: 02/20/2024]
Abstract
BACKGROUND The effects of a solitary neonatal exposure to anesthesia plus surgery (anesthesia/surgery) on cognitive function and the underlying mechanism in developing brains remains largely undetermined. We, therefore, set out to investigate the impact of single exposure to anesthesia/surgery in neonatal mice. METHODS Six-day-old male and female mice received abdominal surgery under 3% sevoflurane plus 50% oxygen for 2 h. The new object recognition (NOR) and Morris water maze (MWM) were used to evaluate cognitive function in young adult mice. Western blot, ELISA and RT-PCR were used to measure levels of NR2B and IL-6 in medial prefrontal cortex and IL-6 in blood of the mice. We employed NR2B siRNA and IL-6 antibody in the interaction studies. RESULTS The anesthesia/surgery decreased the ratio of novel time to novel plus familiar time in NOR and the number of platform crossings, but not escape latency, in MWM compared to sham condition. The mice in anesthesia/surgery group had increased NR2B expression in medial prefrontal cortex, and IL-6 amounts in blood and medial prefrontal cortex. Local injection of NR2B siRNA in medial prefrontal cortex alleviated the anesthesia/surgery-induced cognitive impairment. IL-6 antibody mitigated the anesthesia/surgery-induced upregulation of NR2B and cognitive impairment in young adult mice. CONCLUSIONS These results suggest that a single neonatal exposure to anesthesia/surgery causes impairment of memory, but not learning, in young adult mice through IL-6-regulated increases in NR2B concentrations in medial prefrontal cortex, highlighting the need for further research on the underlying mechanisms of anesthesia/surgery's impact on cognitive function in developing brains.
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Affiliation(s)
- Songhua Zhou
- Department of Anesthesiology, The Third Xiangya Hospital, Central South University, No.138, Tongzipo Road, Yuelu District, Changsha, Hunan, 410013, China; Hunan Province Key Laboratory of Brain Homeostasis, The Third Xiangya Hospital, Central South University, No.138, Tongzipo Road, Yuelu District, Changsha, Hunan, 410013, China
| | - Xiaoyu Cui
- Department of Anesthesiology, The Third Xiangya Hospital, Central South University, No.138, Tongzipo Road, Yuelu District, Changsha, Hunan, 410013, China; Hunan Province Key Laboratory of Brain Homeostasis, The Third Xiangya Hospital, Central South University, No.138, Tongzipo Road, Yuelu District, Changsha, Hunan, 410013, China
| | - Jie Chen
- Department of Anesthesiology, The Third Xiangya Hospital, Central South University, No.138, Tongzipo Road, Yuelu District, Changsha, Hunan, 410013, China; Hunan Province Key Laboratory of Brain Homeostasis, The Third Xiangya Hospital, Central South University, No.138, Tongzipo Road, Yuelu District, Changsha, Hunan, 410013, China
| | - Manli Luo
- Department of Anesthesiology, The Third Xiangya Hospital, Central South University, No.138, Tongzipo Road, Yuelu District, Changsha, Hunan, 410013, China; Hunan Province Key Laboratory of Brain Homeostasis, The Third Xiangya Hospital, Central South University, No.138, Tongzipo Road, Yuelu District, Changsha, Hunan, 410013, China
| | - Wen Ouyang
- Department of Anesthesiology, The Third Xiangya Hospital, Central South University, No.138, Tongzipo Road, Yuelu District, Changsha, Hunan, 410013, China; Hunan Province Key Laboratory of Brain Homeostasis, The Third Xiangya Hospital, Central South University, No.138, Tongzipo Road, Yuelu District, Changsha, Hunan, 410013, China
| | - Jianbin Tong
- Department of Anesthesiology, The Third Xiangya Hospital, Central South University, No.138, Tongzipo Road, Yuelu District, Changsha, Hunan, 410013, China; Hunan Province Key Laboratory of Brain Homeostasis, The Third Xiangya Hospital, Central South University, No.138, Tongzipo Road, Yuelu District, Changsha, Hunan, 410013, China
| | - Zhongcong Xie
- Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA, USA, 02129-2060
| | - Yuan Le
- Department of Anesthesiology, The Third Xiangya Hospital, Central South University, No.138, Tongzipo Road, Yuelu District, Changsha, Hunan, 410013, China; Hunan Province Key Laboratory of Brain Homeostasis, The Third Xiangya Hospital, Central South University, No.138, Tongzipo Road, Yuelu District, Changsha, Hunan, 410013, China.
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13
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Severino L, Kim J, Nam MH, McHugh TJ. From synapses to circuits: What mouse models have taught us about how autism spectrum disorder impacts hippocampal function. Neurosci Biobehav Rev 2024; 158:105559. [PMID: 38246230 DOI: 10.1016/j.neubiorev.2024.105559] [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: 11/29/2023] [Revised: 01/16/2024] [Accepted: 01/17/2024] [Indexed: 01/23/2024]
Abstract
Autism spectrum disorder (ASD) is a complex neurodevelopmental disorder that impacts a variety of cognitive and behavioral domains. While a genetic component of ASD has been well-established, none of the numerous syndromic genes identified in humans accounts for more than 1% of the clinical patients. Due to this large number of target genes, numerous mouse models of the disorder have been generated. However, the focus on distinct brain circuits, behavioral phenotypes and diverse experimental approaches has made it difficult to synthesize the overwhelming number of model animal studies into concrete throughlines that connect the data across levels of investigation. Here we chose to focus on one circuit, the hippocampus, and one hypothesis, a shift in excitatory/inhibitory balance, to examine, from the level of the tripartite synapse up to the level of in vivo circuit activity, the key commonalities across disparate models that can illustrate a path towards a better mechanistic understanding of ASD's impact on hippocampal circuit function.
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Affiliation(s)
- Leandra Severino
- Brain Science Institute, Korea Institute of Science and Technology (KIST), Seoul, South Korea; Division of Bio-Medical Science & Technology, KIST-School, University of Science and Technology, Seoul, South Korea
| | - Jinhyun Kim
- Brain Science Institute, Korea Institute of Science and Technology (KIST), Seoul, South Korea; Division of Bio-Medical Science & Technology, KIST-School, University of Science and Technology, Seoul, South Korea
| | - Min-Ho Nam
- Brain Science Institute, Korea Institute of Science and Technology (KIST), Seoul, South Korea; Division of Bio-Medical Science & Technology, KIST-School, University of Science and Technology, Seoul, South Korea.
| | - Thomas J McHugh
- Brain Science Institute, Korea Institute of Science and Technology (KIST), Seoul, South Korea; Laboratory for Circuit and Behavioral Physiology, RIKEN Center for Brain Science, 2-1 Hirosawa, Wako-shi Saitama, Japan.
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14
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Tretter F, Löffler-Stastka H. Cognitive dissonance and mindset perturbations during crisis: "eco-socio-psycho-somatic" perspectives. World J Psychiatry 2024; 14:215-224. [PMID: 38464764 PMCID: PMC10921281 DOI: 10.5498/wjp.v14.i2.215] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/12/2023] [Revised: 12/08/2023] [Accepted: 01/03/2024] [Indexed: 02/06/2024] Open
Abstract
Mandatory and restrictive health regulations during the corona pandemic caused psychic disorders in many people, which even led to clinically relevant mental disorders. At the same time, there was gradually a polarization of opinions among the population. In order to improve future pandemic management, an integrative understanding of these psychosocial processes therefore seems useful. Here we start theoretically with the mental effects of inconsistencies of the information environment by referring to concepts such as the theory of cognitive dissonance. In a next step, we use the psychodynamic theory to understand the affective-motivational defense mechanisms underlying these cognitive states and processes. However, a broader theoretical framework of psychoanalysis seems to make sense, because self-referential processing also influences the style of thinking. For this reason, we use a more comprehensive psychological systems theoretical framework model to integrate these different perspectives. This integrative view refers in part to basic knowledge of health psychology regarding the resistance of unhealthy ways of thinking and behaviors and the possibilities for interventions for change. We then extend this model to a broader picture that also covers the relationship between men and their environment. This results in the perspective of a multidimensional socioecological theoretical framework, which as a heuristic reference model and related to other ecological approaches could also be helpful for various theoretical questions for public health, and could provide a better public understanding of health issues. In line with this perspective, we hypothesize that with regard to the coronavirus disease 2019 pandemic, the acceptance of public health narratives could be increased if a more consistent picture of the scientific descriptions and explanations of the pandemic - similar to the model proposed - could be provided, which would enable the understanding of the origin, course and countermeasures, and thus could have positive collective psycho-hygienic effects.
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Affiliation(s)
- Felix Tretter
- Department of Systems Medicine and Healthcare Systems, Bertalanffy Center for the Study of Systems Science, Vienna 1040, Austria
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15
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Kawamoto M, Takagishi H, Ishihara T, Takagi S, Kanai R, Sugihara G, Takahashi H, Matsuda T. Hippocampal volume mediates the relationship of parental rejection in childhood with social cognition in healthy adults. Sci Rep 2023; 13:19167. [PMID: 37932349 PMCID: PMC10628272 DOI: 10.1038/s41598-023-46512-2] [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: 03/13/2023] [Accepted: 11/01/2023] [Indexed: 11/08/2023] Open
Abstract
Childhood abuse reduces hippocampal and amygdala volumes and impairs social cognition, including the ability to recognize facial expressions. However, these associations have been studied primarily in individuals with a history of severe abuse and psychiatric symptoms; researchers have not determined whether these associations can also be observed in healthy adults. In the present study, we analyzed data from 400 healthy adults (208 men and 192 women) at Tamagawa University. Parental rejection reflecting childhood abuse was assessed using the short form of Egna Minnen Beträffande Uppfostran, while social cognition was assessed using the "Fake Smile Detection Task." Hippocampal and amygdala volumes were extracted from T1-weighted magnetic resonance imaging data using FreeSurfer. We found that greater parental rejection resulted in smaller hippocampal and amygdala volumes and poorer performance in the Fake Smile Detection Task. Structural equation modeling analysis supported the model that hippocampal volume mediates maternal rejection effect on performance on the Fake Smile Detection Task, with involvement of the amygdala. These findings are in line with the structural and functional connectivity found between the hippocampus and amygdala and their joint involvement in social cognition. Therefore, parental rejection may affect hippocampal and amygdala volumes and social cognitive function even in symptom-free adults.
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Affiliation(s)
- Marino Kawamoto
- Department of Psychiatry and Behavioral Sciences, Tokyo Medical and Dental University Graduate School, Tokyo, Japan
- Tamagawa University Brain Science Institute, Tokyo, Japan
| | | | - Toru Ishihara
- Graduate School of Human Development and Environment, Kobe University, Kobe, Japan
| | - Shunsuke Takagi
- Department of Psychiatry and Behavioral Sciences, Tokyo Medical and Dental University Graduate School, Tokyo, Japan
| | | | - Genichi Sugihara
- Department of Psychiatry and Behavioral Sciences, Tokyo Medical and Dental University Graduate School, Tokyo, Japan
| | - Hidehiko Takahashi
- Department of Psychiatry and Behavioral Sciences, Tokyo Medical and Dental University Graduate School, Tokyo, Japan
- Tamagawa University Brain Science Institute, Tokyo, Japan
- Center for Brain Integration Research, Tokyo Medical and Dental University, Tokyo, Japan
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16
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Kirkland JM, Edgar EL, Patel I, Kopec AM. Impaired microglia-mediated synaptic pruning in the nucleus accumbens during adolescence results in persistent dysregulation of familiar, but not novel social interactions in sex-specific ways. BIORXIV : THE PREPRINT SERVER FOR BIOLOGY 2023:2023.05.02.539115. [PMID: 37205324 PMCID: PMC10187149 DOI: 10.1101/2023.05.02.539115] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/21/2023]
Abstract
Evolutionarily conserved, peer-directed social behaviors are essential to participate in many aspects of human society. These behaviors directly impact psychological, physiological, and behavioral maturation. Adolescence is an evolutionarily conserved period during which reward-related behaviors, including social behaviors, develop via developmental plasticity in the mesolimbic dopaminergic 'reward' circuitry of the brain. The nucleus accumbens (NAc) is an intermediate reward relay center that develops during adolescence and mediates both social behaviors and dopaminergic signaling. In several developing brain regions, synaptic pruning mediated by microglia, the resident immune cells of the brain, is important for normal behavioral development. In rats, we previously demonstrated that microglial synaptic pruning also mediates NAc and social development during sex-specific adolescent periods and via sex-specific synaptic pruning targets. In this report, we demonstrate that interrupting microglial pruning in NAc during adolescence persistently dysregulates social behavior towards a familiar, but not novel social partner in both sexes, via sex-specific behavioral expression. This leads us to infer that naturally occurring NAc pruning serves to reduce social behaviors primarily directed toward a familiar conspecific in both sexes, but in sex-specific ways.
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Affiliation(s)
- Julia M. Kirkland
- Department of Neuroscience and Experimental Therapeutics, Albany Medical College
| | - Erin L. Edgar
- Department of Neuroscience and Experimental Therapeutics, Albany Medical College
| | - Ishan Patel
- Department of Neuroscience and Experimental Therapeutics, Albany Medical College
| | - Ashley M. Kopec
- Department of Neuroscience and Experimental Therapeutics, Albany Medical College
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17
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Walsh JJ, Christoffel DJ, Malenka RC. Neural circuits regulating prosocial behaviors. Neuropsychopharmacology 2023; 48:79-89. [PMID: 35701550 PMCID: PMC9700801 DOI: 10.1038/s41386-022-01348-8] [Citation(s) in RCA: 30] [Impact Index Per Article: 15.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/13/2022] [Revised: 05/09/2022] [Accepted: 05/17/2022] [Indexed: 11/09/2022]
Abstract
Positive, prosocial interactions are essential for survival, development, and well-being. These intricate and complex behaviors are mediated by an amalgamation of neural circuit mechanisms working in concert. Impairments in prosocial behaviors, which occur in a large number of neuropsychiatric disorders, result from disruption of the coordinated activity of these neural circuits. In this review, we focus our discussion on recent findings that utilize modern approaches in rodents to map, monitor, and manipulate neural circuits implicated in a variety of prosocial behaviors. We highlight how modulation by oxytocin, serotonin, and dopamine of excitatory and inhibitory synaptic transmission in specific brain regions is critical for regulation of adaptive prosocial interactions. We then describe how recent findings have helped elucidate pathophysiological mechanisms underlying the social deficits that accompany neuropsychiatric disorders. We conclude by discussing approaches for the development of more efficacious and targeted therapeutic interventions to ameliorate aberrant prosocial behaviors.
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Affiliation(s)
- Jessica J Walsh
- Department of Pharmacology, University of North Carolina, Chapel Hill, NC, 27514, USA.
- Carolina Institute for Developmental Disabilities, University of North Carolina, Chapel Hill, NC, USA.
- Neuroscience Center, University of North Carolina, Chapel Hill, NC, 27514, USA.
| | - Daniel J Christoffel
- Neuroscience Center, University of North Carolina, Chapel Hill, NC, 27514, USA
- Department of Psychology and Neuroscience, University of North Carolina, Chapel Hill, NC, 27514, USA
| | - Robert C Malenka
- Nancy Pritzker Laboratory, Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford, CA, 94305-5453, USA.
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18
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High Morphine Use Disorder Susceptibility Is Predicted by Impaired Learning Ability in Mice. Brain Sci 2022; 12:brainsci12121650. [PMID: 36552110 PMCID: PMC9776386 DOI: 10.3390/brainsci12121650] [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: 09/24/2022] [Revised: 10/24/2022] [Accepted: 11/24/2022] [Indexed: 12/05/2022] Open
Abstract
An obvious reason for substance uses disorders (SUDs) is drug craving and seeking behavior induced by conditioned context, which is an abnormal solid context memory. The relationship between susceptibility to SUD and learning ability remains unclear in humans and animal models. In this study, we found that susceptibility to morphine use disorder (MUD) was negatively correlated with learning ability in conditioned place preference (CPP) in C57 mice. By using behavioral tests, we identified the FVB mouse as learning impaired. In addition, we discovered that learning-relevant proteins, such as the glutamate receptor subunits GluA1, NR1, and NR2A, were decreased in FVB mice. Finally, we assessed the context learning ability of FVB mice using the CPP test and priming. We found that FVB mice had lower learning performance with respect to normal memory but higher performance of morphine-reinstatement memory. Compared to C57 mice, FVB mice are highly sensitive to MUDs. Our results suggest that SUD susceptibility is predicted by impaired learning ability in mice; therefore, learning ability can play a simple and practical role in identifying high-risk SUD groups.
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19
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Wang Z, Zhang Y, Feng W, Pang Y, Chen S, Ding S, Chen Y, Sheng C, Marshall C, Shi J, Xiao M. Miconazole Promotes Cooperative Ability of a Mouse Model of Alzheimer Disease. Int J Neuropsychopharmacol 2022; 25:951-967. [PMID: 36112386 PMCID: PMC9670758 DOI: 10.1093/ijnp/pyac061] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/30/2022] [Revised: 08/10/2022] [Accepted: 09/08/2022] [Indexed: 01/07/2023] Open
Abstract
BACKGROUND Cooperative defect is 1 of the earliest manifestations of disease patients with Alzheimer disease (AD) exhibit, but the underlying mechanism remains unclear. METHODS We evaluated the cooperative function of APP/PS1 transgenic AD model mice at ages 2, 5, and 8 months by using a cooperative drinking task. We examined neuropathologic changes in the medial prefrontal cortex (mPFC). Another experiment was designed to observe whether miconazole, which has a repairing effect on myelin sheath, could promote the cooperative ability of APP/PS1 mice in the early AD-like stage. We also investigated the protective effects of miconazole on cultured mouse cortical oligodendrocytes exposed to human amyloid β peptide (Aβ1-42). RESULTS We observed an age-dependent impairment of cooperative water drinking behavior in APP/PS1 mice. The AD mice with cooperative dysfunction showed decreases in myelin sheath thickness, oligodendrocyte nuclear heterochromatin percentage, and myelin basic protein expression levels in the mPFC. The cooperative ability was significantly improved in APP/PS1 mice treated with miconazole. Miconazole treatment increased oligodendrocyte maturation and myelin sheath thickness without reducing Aβ plaque deposition, reactive gliosis, and inflammatory factor levels in the mPFC. Miconazole also protected cultured oligodendrocytes from the toxicity of Aβ1-42. CONCLUSIONS These results demonstrate that mPFC hypomyelination is involved in the cooperative deficits of APP/PS1 mice. Improving myelination through miconazole therapy may offer a potential therapeutic approach for early intervention in AD.
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Affiliation(s)
| | | | - Weixi Feng
- Jiangsu Province Key Laboratory of Neurodegeneration, Center for Global Health, Nanjing Medical University, Nanjing, China,Brain Institute, the Affiliated Nanjing Brain Hospital of Nanjing Medical University, Nanjing, China
| | - Yingting Pang
- Jiangsu Province Key Laboratory of Neurodegeneration, Center for Global Health, Nanjing Medical University, Nanjing, China,Brain Institute, the Affiliated Nanjing Brain Hospital of Nanjing Medical University, Nanjing, China
| | - Sijia Chen
- Jiangsu Province Key Laboratory of Neurodegeneration, Center for Global Health, Nanjing Medical University, Nanjing, China,Brain Institute, the Affiliated Nanjing Brain Hospital of Nanjing Medical University, Nanjing, China
| | - Shixin Ding
- Jiangsu Province Key Laboratory of Neurodegeneration, Center for Global Health, Nanjing Medical University, Nanjing, China,Brain Institute, the Affiliated Nanjing Brain Hospital of Nanjing Medical University, Nanjing, China
| | - Yan Chen
- Jiangsu Province Key Laboratory of Neurodegeneration, Center for Global Health, Nanjing Medical University, Nanjing, China,Brain Institute, the Affiliated Nanjing Brain Hospital of Nanjing Medical University, Nanjing, China
| | - Chengyu Sheng
- Jiangsu Province Key Laboratory of Neurodegeneration, Center for Global Health, Nanjing Medical University, Nanjing, China
| | - Charles Marshall
- Department of Rehabilitation Sciences, University of Kentucky Center of Excellence in Rural Health, Hazard, USA
| | - Jingping Shi
- Brain Institute, the Affiliated Nanjing Brain Hospital of Nanjing Medical University, Nanjing, China,Department of Neurology, the Affiliated Nanjing Brain Hospital of Nanjing Medical University, Nanjing, China
| | - Ming Xiao
- Correspondence: Ming Xiao, MD, PhD, Jiangsu Key Laboratory of Neurodegeneration, Nanjing Medical University, No. 101 Longmian Ave, Nanjing 211166, China ()
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20
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Lemonnier C, Bize P, Boonstra R, Dobson FS, Criscuolo F, Viblanc VA. Effects of the social environment on vertebrate fitness and health in nature: Moving beyond the stress axis. Horm Behav 2022; 145:105232. [PMID: 35853411 DOI: 10.1016/j.yhbeh.2022.105232] [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: 03/14/2022] [Revised: 06/04/2022] [Accepted: 06/22/2022] [Indexed: 11/22/2022]
Abstract
Social interactions are a ubiquitous feature of the lives of vertebrate species. These may be cooperative or competitive, and shape the dynamics of social systems, with profound effects on individual behavior, physiology, fitness, and health. On one hand, a wealth of studies on humans, laboratory animal models, and captive species have focused on understanding the relationships between social interactions and individual health within the context of disease and pathology. On the other, ecological studies are attempting an understanding of how social interactions shape individual phenotypes in the wild, and the consequences this entails in terms of adaptation. Whereas numerous studies in wild vertebrates have focused on the relationships between social environments and the stress axis, much remains to be done in understanding how socially-related activation of the stress axis coordinates other key physiological functions related to health. Here, we review the state of our current knowledge on the effects that social interactions may have on other markers of vertebrate fitness and health. Building upon complementary findings from the biomedical and ecological fields, we identify 6 key physiological functions (cellular metabolism, oxidative stress, cellular senescence, immunity, brain function, and the regulation of biological rhythms) which are intimately related to the stress axis, and likely directly affected by social interactions. Our goal is a holistic understanding of how social environments affect vertebrate fitness and health in the wild. Whereas both social interactions and social environments are recognized as important sources of phenotypic variation, their consequences on vertebrate fitness, and the adaptive nature of social-stress-induced phenotypes, remain unclear. Social flexibility, or the ability of an animal to change its social behavior with resulting changes in social systems in response to fluctuating environments, has emerged as a critical underlying factor that may buffer the beneficial and detrimental effects of social environments on vertebrate fitness and health.
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Affiliation(s)
- Camille Lemonnier
- Ecole Normale Supérieur de Lyon, 69342 Lyon, France; Université de Strasbourg, CNRS, IPHC UMR 7178, 67000 Strasbourg, France.
| | - Pierre Bize
- School of Biological Sciences, University of Aberdeen, Aberdeen, UK; Swiss Institute of Ornithology, Sempach, Switzerland
| | - Rudy Boonstra
- Department of Biological Sciences, University of Toronto Scarborough, Toronto, Canada
| | - F Stephen Dobson
- Université de Strasbourg, CNRS, IPHC UMR 7178, 67000 Strasbourg, France; Department of Biological Sciences, Auburn University, Auburn, AL, USA
| | | | - Vincent A Viblanc
- Université de Strasbourg, CNRS, IPHC UMR 7178, 67000 Strasbourg, France
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21
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Baerends E, Soud K, Folke J, Pedersen AK, Henmar S, Konrad L, Lycas MD, Mori Y, Pakkenberg B, Woldbye DPD, Dmytriyeva O, Pankratova S. Modeling the early stages of Alzheimer's disease by administering intracerebroventricular injections of human native Aβ oligomers to rats. Acta Neuropathol Commun 2022; 10:113. [PMID: 35974377 PMCID: PMC9380371 DOI: 10.1186/s40478-022-01417-5] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/23/2022] [Accepted: 07/29/2022] [Indexed: 11/10/2022] Open
Abstract
Alzheimer's disease (AD) is a progressive and irreversible neurodegenerative disease characterized by the accumulation of aggregated amyloid beta (Aβ) and hyperphosphorylated tau along with a slow decline in cognitive functions. Unlike advanced AD, the initial steps of AD pathophysiology have been poorly investigated, partially due to limited availability of animal models focused on the early, plaque-free stages of the disease. The aim of this study was to evaluate the early behavioral, anatomical and molecular alterations in wild-type rats following intracerebroventricular injections of human Aβ oligomers (AβOs). Bioactive human AD and nondemented control brain tissue extracts were characterized using ELISA and proteomics approaches. Following a bilateral infusion, rats underwent behavioral testing, including the elevated plus maze, social recognition test, Morris water maze and Y-maze within 6 weeks postinjection. An analysis of brain structure was performed with manganese-enhanced MRI. Collected brain tissues were analyzed using stereology, immunohistochemistry, ELISA and qPCR. No sensorimotor deficits affecting motor performance on different maze tasks were observed, nor was spatial memory disturbed in AD rats. In contrast, a significant impairment of social memory became evident at 21 days postinjection. This deficit was associated with a significantly decreased volume of the lateral entorhinal cortex and a tendency toward a decrease in the total brain volume. Significant increase of cleaved caspase-3-positive cells, microglial activation and proinflammatory responses accompanied by altered expression of synaptic markers were observed in the hippocampus of AD rats with immunohistochemical and qPCR approaches at 6 weeks postinjection. Our data suggest that the social memory impairment observed in AβO-injected rats might be determined by neuroinflammatory responses and synaptopathy. An infusion of native oligomeric Aβ in the rat brain represents a feasible tool to model early plaque-free events associated with AD.
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Affiliation(s)
- Eva Baerends
- Department of Neuroscience, Faculty of Health and Medical Sciences, University of Copenhagen, 2200, Copenhagen, Denmark
| | - Katia Soud
- Department of Neuroscience, Faculty of Health and Medical Sciences, University of Copenhagen, 2200, Copenhagen, Denmark
| | - Jonas Folke
- Centre for Neuroscience and Stereology, Department of Neurology,, Bispebjerg-Frederiksberg Hospital, Copenhagen University Hospital, Copenhagen, Denmark.,Copenhagen Center for Translational Research, Bispebjerg-Frederiksberg Hospital, Copenhagen University Hospital, Copenhagen, Denmark
| | - Anna-Kathrine Pedersen
- Proteomics Program, Novo Nordisk Foundation Center for Protein Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
| | - Simon Henmar
- Department of Neuroscience, Faculty of Health and Medical Sciences, University of Copenhagen, 2200, Copenhagen, Denmark
| | - Lisa Konrad
- Department of Neuroscience, Faculty of Health and Medical Sciences, University of Copenhagen, 2200, Copenhagen, Denmark
| | - Matthew D Lycas
- Department of Neuroscience, Faculty of Health and Medical Sciences, University of Copenhagen, 2200, Copenhagen, Denmark
| | - Yuki Mori
- Center for Translational Neuromedicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
| | - Bente Pakkenberg
- Centre for Neuroscience and Stereology, Department of Neurology,, Bispebjerg-Frederiksberg Hospital, Copenhagen University Hospital, Copenhagen, Denmark.,Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
| | - David P D Woldbye
- Department of Neuroscience, Faculty of Health and Medical Sciences, University of Copenhagen, 2200, Copenhagen, Denmark
| | - Oksana Dmytriyeva
- Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
| | - Stanislava Pankratova
- Department of Neuroscience, Faculty of Health and Medical Sciences, University of Copenhagen, 2200, Copenhagen, Denmark. .,Comparative Pediatrics and Nutrition, Department of Veterinary and Animal Sciences, University of Copenhagen, Copenhagen, Denmark.
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22
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Potrebić M, Pavković Ž, Puškaš N, Pešić V. The Influence of Social Isolation on Social Orientation, Sociability, Social Novelty Preference, and Hippocampal Parvalbumin-Expressing Interneurons in Peripubertal Rats - Understanding the Importance of Meeting Social Needs in Adolescence. Front Behav Neurosci 2022; 16:872628. [PMID: 35592640 PMCID: PMC9113078 DOI: 10.3389/fnbeh.2022.872628] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/09/2022] [Accepted: 03/28/2022] [Indexed: 11/13/2022] Open
Abstract
The fulfillment of belonging needs underlies a variety of behaviors. In order to understand how social needs unmet during maturation shape everyday life, we examined social motivation and cognition in peripubertal rats, as a rodent model of adolescence, subjected to social isolation (SI) during early and early-to-mid adolescence. The behavioral correlates of social orientation (social space preference), sociability (preference for social over non-social novelty), and social novelty preference (SNP) were examined in group-housed (GH) and single-housed (SH) rats in a 3-chamber test. The response to social odors was examined to gain insights into the developmental role of social odors in motivated social behavior. Differentiation between appetitive (number of visits/approaches) and consummatory (exploratory time) aspects of motivated social behavior was done to determine which facet of social motivation characterizes maturation when social needs are met and which aspect dominates when social needs are unsatisfied. The SI-sensitive parvalbumin-expressing interneurons (PVI) in the hippocampus were examined using immunohistochemistry. The main findings are the following: (1) in GH rats, the preference for social space is not evident regardless of animals' age, while sociability becomes apparent in mid-adolescence strictly through consummatory behavior, along with complete SNP (appetitive, consummatory); (2) SH promotes staying in a social chamber/space regardless of animals' age and produces an appetitive preference for it only in early-adolescent animals; (3) SH promotes sociability (appetitive, consummatory) regardless of the animals' age and prevents the SNP; (4) the preference for a social odor is displayed in all the groups through consummatory behavior, while appetitive behavior is evident only in SH rats; (5) the response to social odors does not commensurate directly to the response to conspecifics; (6) SH does not influence PVI in the hippocampus, except in the case of early-adolescence when a transient decrease in the dentate gyrus is observed. These results accentuate the developmental complexity of social motivation and cognition, and the power of SI in adolescence to infringe social maturation at different functional levels, promoting appetitive behavior toward peers overall but harming the interest for social novelty. The findings emphasize the importance of the fulfillment of basic social needs in the navigation through the social world.
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Affiliation(s)
- Milica Potrebić
- Molecular Neurobiology and Behavior, Department of Neurobiology, Institute for Biological Research “Siniša Stanković”, National Institute of Republic of Serbia, University of Belgrade, Belgrade, Serbia
| | - Željko Pavković
- Molecular Neurobiology and Behavior, Department of Neurobiology, Institute for Biological Research “Siniša Stanković”, National Institute of Republic of Serbia, University of Belgrade, Belgrade, Serbia
| | - Nela Puškaš
- Institute of Histology and Embryology “Aleksandar Đ. Kostić”, Faculty of Medicine, University of Belgrade, Belgrade, Serbia
| | - Vesna Pešić
- Molecular Neurobiology and Behavior, Department of Neurobiology, Institute for Biological Research “Siniša Stanković”, National Institute of Republic of Serbia, University of Belgrade, Belgrade, Serbia
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23
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The Novel Analogue of Modafinil CE-158 Protects Social Memory against Interference and Triggers the Release of Dopamine in the Nucleus Accumbens of Mice. Biomolecules 2022; 12:biom12040506. [PMID: 35454095 PMCID: PMC9033101 DOI: 10.3390/biom12040506] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/03/2022] [Revised: 03/10/2022] [Accepted: 03/24/2022] [Indexed: 11/28/2022] Open
Abstract
Previous studies have shown that atypical dopamine-transporter-inhibitors such as modafinil and its analogues modify behavioral and cognitive functions in rodents. Here, we tested potential promnestic effects of the novel, more dopamine-transporter selective modafinil analogue CE-158 in the social discrimination memory task in male mice. Systemic administration of CE-158 1 h before the social learning event prevented the impairment of social-recognition memory following retroactive interference 3 h after the learning session of a juvenile conspecific. This effect was dose-dependent, as mice treated with 10 mg/kg, but not with 1 mg/kg CE-158, were able to discriminate between the novel and familiar conspecific despite the presentation of an interference stimulus, both 3 h and 6 h post learning. However, when 10 mg/kg of the drug was administered after learning, CE-158 failed to prevent social memory from interference. Paralleling these behavioral effects, the systemic administration of 10 mg/kg CE-158 caused a rapid and sustained elevation of extracellular dopamine in the nucleus accumbens, a brain area where dopaminergic signaling plays a key role in learning and memory function, of freely moving mice, while 1 mg/kg was not sufficient for altering dopamine levels. Taken together, our findings suggest promnestic effects of the novel dopamine-transporter-inhibitor CE-158 in a social recognition memory test that may be in part mediated via increased dopamine-neurotransmission in the nucleus accumbens. Thus, selective-dopamine-transporter-inhibitors such as CE-158 may represent interesting drug candidates for the treatment of memory complaints observed in humans with cognitive impairments and dementia.
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24
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Fuentes I, Morishita Y, Gonzalez-Salinas S, Champagne FA, Uchida S, Shumyatsky GP. Experience-Regulated Neuronal Signaling in Maternal Behavior. Front Mol Neurosci 2022; 15:844295. [PMID: 35401110 PMCID: PMC8987921 DOI: 10.3389/fnmol.2022.844295] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/27/2021] [Accepted: 02/28/2022] [Indexed: 11/13/2022] Open
Abstract
Maternal behavior is shaped and challenged by the changing developmental needs of offspring and a broad range of environmental factors, with evidence indicating that the maternal brain exhibits a high degree of plasticity. This plasticity is displayed within cellular and molecular systems, including both intra- and intercellular signaling processes as well as transcriptional profiles. This experience-associated plasticity may have significant overlap with the mechanisms controlling memory processes, in particular those that are activity-dependent. While a significant body of work has identified various molecules and intracellular processes regulating maternal care, the role of activity- and experience-dependent processes remains unclear. We discuss recent progress in studying activity-dependent changes occurring at the synapse, in the nucleus, and during the transport between these two structures in relation to maternal behavior. Several pre- and postsynaptic molecules as well as transcription factors have been found to be critical in these processes. This role reflects the principal importance of the molecular and cellular mechanisms of memory formation to maternal and other behavioral adaptations.
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Affiliation(s)
- Ileana Fuentes
- Department of Genetics, Rutgers University, Piscataway, NJ, United States
| | | | | | - Frances A. Champagne
- Department of Psychology, University of Texas at Austin, Austin, TX, United States
| | - Shusaku Uchida
- SK Project, Medical Innovation Center, Kyoto University Graduate School of Medicine, Kyoto, Japan
| | - Gleb P. Shumyatsky
- Department of Genetics, Rutgers University, Piscataway, NJ, United States
- *Correspondence: Gleb P. Shumyatsky
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25
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Arzy S, Kaplan R. Transforming Social Perspectives with Cognitive Maps. Soc Cogn Affect Neurosci 2022; 17:939-955. [PMID: 35257155 PMCID: PMC9527473 DOI: 10.1093/scan/nsac017] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/30/2021] [Revised: 12/17/2021] [Accepted: 03/07/2022] [Indexed: 01/29/2023] Open
Abstract
Growing evidence suggests that cognitive maps represent relations between social knowledge similar to how spatial locations are represented in an environment. Notably, the extant human medial temporal lobe literature assumes associations between social stimuli follow a linear associative mapping from an egocentric viewpoint to a cognitive map. Yet, this form of associative social memory doesn't account for a core phenomenon of social interactions in which social knowledge learned via comparisons to the self, other individuals, or social networks are assimilated within a single frame of reference. We argue that hippocampal-entorhinal coordinate transformations, known to integrate egocentric and allocentric spatial cues, inform social perspective switching between the self and others. We present evidence that the hippocampal formation helps inform social interactions by relating self versus other social attribute comparisons to society in general, which can afford rapid and flexible assimilation of knowledge about the relationship between the self and social networks of varying proximities. We conclude by discussing the ramifications of cognitive maps in aiding this social perspective transformation process in states of health and disease.
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Affiliation(s)
- Shahar Arzy
- Faculty of Medicine and the Department of Cognitive Sciences, Hebrew University of Jerusalem, Jerusalem 91120, Israel
- Department of Neurology, Hadassah Hebrew University Medical School, Jerusalem 91120, Israel
| | - Raphael Kaplan
- Correspondence should be addressed to Raphael Kaplan, Department of Basic Psychology, Clinical Psychology, and Psychobiology, Universitat Jaume I, Avinguda de Vicent Sos Baynat, Castelló de la Plana, Spain. E-mail:
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26
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Ohana O, Alberini CM, Donato F. Introduction to the special issue on the ontogeny of hippocampal functions. Hippocampus 2022; 32:69-72. [PMID: 35005808 PMCID: PMC9303776 DOI: 10.1002/hipo.23406] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/24/2022]
Affiliation(s)
- Ora Ohana
- Institute for Molecular and Cellular Cognition, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | | | - Flavio Donato
- Biozentrum of the University of Basel, Basel, Switzerland
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27
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Kenwood MM, Kalin NH, Barbas H. The prefrontal cortex, pathological anxiety, and anxiety disorders. Neuropsychopharmacology 2022; 47:260-275. [PMID: 34400783 PMCID: PMC8617307 DOI: 10.1038/s41386-021-01109-z] [Citation(s) in RCA: 142] [Impact Index Per Article: 47.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/08/2021] [Revised: 07/06/2021] [Accepted: 07/08/2021] [Indexed: 02/07/2023]
Abstract
Anxiety is experienced in response to threats that are distal or uncertain, involving changes in one's subjective state, autonomic responses, and behavior. Defensive and physiologic responses to threats that involve the amygdala and brainstem are conserved across species. While anxiety responses typically serve an adaptive purpose, when excessive, unregulated, and generalized, they can become maladaptive, leading to distress and avoidance of potentially threatening situations. In primates, anxiety can be regulated by the prefrontal cortex (PFC), which has expanded in evolution. This prefrontal expansion is thought to underlie primates' increased capacity to engage high-level regulatory strategies aimed at coping with and modifying the experience of anxiety. The specialized primate lateral, medial, and orbital PFC sectors are connected with association and limbic cortices, the latter of which are connected with the amygdala and brainstem autonomic structures that underlie emotional and physiological arousal. PFC pathways that interface with distinct inhibitory systems within the cortex, the amygdala, or the thalamus can regulate responses by modulating neuronal output. Within the PFC, pathways connecting cortical regions are poised to reduce noise and enhance signals for cognitive operations that regulate anxiety processing and autonomic drive. Specialized PFC pathways to the inhibitory thalamic reticular nucleus suggest a mechanism to allow passage of relevant signals from thalamus to cortex, and in the amygdala to modulate the output to autonomic structures. Disruption of specific nodes within the PFC that interface with inhibitory systems can affect the negative bias, failure to regulate autonomic arousal, and avoidance that characterize anxiety disorders.
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Affiliation(s)
- Margaux M Kenwood
- Department of Psychiatry, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA
- Neuroscience Training Program at University of Wisconsin-Madison, Madison, USA
| | - Ned H Kalin
- Department of Psychiatry, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA
- Neuroscience Training Program at University of Wisconsin-Madison, Madison, USA
- Wisconsin National Primate Center, Madison, WI, USA
| | - Helen Barbas
- Neural Systems Laboratory, Department of Health Sciences, Boston University, Boston, MA, USA.
- Department of Anatomy and Neurobiology, Boston University School of Medicine, Boston, MA, USA.
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28
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Tang Q, Guo Q, Li K, Fei F. VRT-043198 Ameliorates Surgery-Induced Neurocognitive Disorders by Restoring the NGF and BNDF Expression in Aged Mice. Neuropsychiatr Dis Treat 2022; 18:1027-1037. [PMID: 35607505 PMCID: PMC9123246 DOI: 10.2147/ndt.s364250] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/01/2022] [Accepted: 05/06/2022] [Indexed: 11/23/2022] Open
Abstract
BACKGROUND Perioperative neurocognitive disorders (PND) are common surgical complications in the elderly. Pyroptosis-associated inflammation has been suggested to participate in a series of neurocognitive diseases, including Alzheimer's disease. Given that VRT-043198 can reportedly inhibit caspase-1-induced pyroptosis, this study sought to determine whether VRT-043198 reduced PND in a mouse model following abdominal exploratory laparotomy. METHODS 20-month-old male C57/BL mice were used to establish an abdominal exploratory laparotomy (AEL) model of PND. VRT-043198 (1, 10 and 100 mg/kg) was administered intraperitoneally immediately after surgery. Thirty days post-surgery, the mice were evaluated in the Morris water maze test. Their number of neurons, neurotrophin nerve growth factor (NGF) levels and brain-derived neurotrophic factor (BDNF) were measured. In the hippocampus, A1-type astrocytes and M1-type microglia were assessed using an immunofluorescence assay and Western blot, respectively. Caspase-1 activity, IL-1β, IL-18, and PPAR-γ were also measured 24h after surgery. RESULTS VRT-043198 administration increased the time to cross the platform and increased the ratio of distance and time in the targeted quadrant after surgery. Furthermore, it was found that VRT-043198 restored neuronal amount, increased NGF and BDNF and decreased the number of A1-type astrocytes and M1-type microglia. VRT-043198 also attenuated caspase-1 activity, downregulated IL-1β and IL-18, but increased PPAR-γ 24h post-surgery. CONCLUSION VRT-043198 improved PND in aged mice after abdominal exploratory laparotomy by restoring the NGF and BNDF expression. These results indicate that VRT-043198 may be a potential therapy for PND.
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Affiliation(s)
- Qi Tang
- Department of Anesthesiology, First People's Hospital of Taicang, Soochow University, Suzhou, Jiangsu Province, People's Republic of China
| | - Qiang Guo
- Department of Anesthesiology, First People's Hospital of Taicang, Soochow University, Suzhou, Jiangsu Province, People's Republic of China
| | - Ke Li
- Department of Anesthesiology, First People's Hospital of Taicang, Soochow University, Suzhou, Jiangsu Province, People's Republic of China
| | - Fan Fei
- Department of Anesthesiology, First People's Hospital of Taicang, Soochow University, Suzhou, Jiangsu Province, People's Republic of China
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Cerebellum, Embodied Emotions, and Psychological Traits. ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY 2022; 1378:255-269. [DOI: 10.1007/978-3-030-99550-8_16] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 10/16/2022]
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30
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Sakurai T. Social processes and social environment during development. Semin Cell Dev Biol 2021; 129:40-46. [PMID: 34649805 DOI: 10.1016/j.semcdb.2021.09.016] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/27/2021] [Revised: 09/20/2021] [Accepted: 09/28/2021] [Indexed: 12/24/2022]
Abstract
Social behavior involves many processes including cognitive functions. Altered social behaviors associated with many psychiatric disorders might have alterations in the processes. Poor social environment affects development and maturation of cognitive functions that are important for social cognition, possibly introducing social stress as well as vulnerability to the stress into the developing brain. Adolescence and early adulthood have higher sensitivity to social stress, which may be linked to the onset of psychiatric disorders during this time period. Understanding social behavioral processes in detail will be crucial for elucidating mechanisms of emerging the social behavior phenotypes in psychiatric disorders and for devising therapeutic and preventive interventions to introduce the resilience for the onset of psychiatric disorders through modulation of social circuitries.
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Affiliation(s)
- Takeshi Sakurai
- Medical Innovation Center Kyoto University Graduate School of Medicine, 53 ShogoinKawahara-cho, Sakyo-ku, Kyoto 606-8507, Japan; Department of Pathology, Columbia University Vagelos College of Physicians and Surgeons, New York, USA.
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31
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Macro- and micro-structural cerebellar and cortical characteristics of cognitive empathy towards fictional characters in healthy individuals. Sci Rep 2021; 11:8804. [PMID: 33888760 PMCID: PMC8062506 DOI: 10.1038/s41598-021-87861-0] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/25/2020] [Accepted: 03/31/2021] [Indexed: 12/21/2022] Open
Abstract
Few investigations have analyzed the neuroanatomical substrate of empathic capacities in healthy subjects, and most of them have neglected the potential involvement of cerebellar structures. The main aim of the present study was to investigate the associations between bilateral cerebellar macro- and micro-structural measures and levels of cognitive and affective trait empathy (measured by Interpersonal Reactivity Index, IRI) in a sample of 70 healthy subjects of both sexes. We also estimated morphometric variations of cerebral Gray Matter structures, to ascertain whether the potential empathy-related peculiarities in cerebellar areas were accompanied by structural differences in other cerebral regions. At macro-structural level, the volumetric differences were analyzed by Voxel-Based Morphometry (VBM)- and Region of Interest (ROI)-based approaches, and at a micro-structural level, we analyzed Diffusion Tensor Imaging (DTI) data, focusing in particular on Mean Diffusivity and Fractional Anisotropy. Fantasy IRI-subscale was found to be positively associated with volumes in right cerebellar Crus 2 and pars triangularis of inferior frontal gyrus. The here described morphological variations of cerebellar Crus 2 and pars triangularis allow to extend the traditional cortico-centric view of cognitive empathy to the cerebellar regions and indicate that in empathizing with fictional characters the cerebellar and frontal areas are co-recruited.
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