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1
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Packard A, Amos JS, Festic E. Effects of daylight savings time transition on compliance and effectiveness of positive airway pressure therapy. Sleep Biol Rhythms 2025; 23:163-169. [PMID: 40190609 PMCID: PMC11971075 DOI: 10.1007/s41105-024-00565-6] [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: 05/05/2024] [Accepted: 12/17/2024] [Indexed: 04/09/2025]
Abstract
Spring transitions into daylight savings time (DST) result in increase of sleep latency and fragmentation and decrease of sleep time and efficiency. We evaluated the effects of DST on patterns of positive airway pressure (PAP) use and its effectiveness by utilizing continuous tracking of PAP therapy available with cloud-based sleep care management systems. 62 compliant adult OSA patients from Jacksonville, Florida, USA on stable continuous PAP (CPAP)/autoPAP (APAP) therapy were enrolled and PAP usage and residual apnea-hypopnea index (AHI) were collected for the "pre-DST period" (Sun-Mon-Tue, 7-9/03/2021) and "DST period" (Sun-Mon-Tue, 14-16/03/2021) from compliance reports generated or downloaded via cloud-based sleep care management systems. Demographic variables, average compliance and effectiveness of PAP during the two weeks that included both intervals of interest (from Wednesday 3rd to Wednesday 17th) were further analyzed. Statistics included repeated measures ANOVA, non-parametric Wilcoxson's rank sum tests, independent and paired T tests, and Chi-square test. Majority of patients were Caucasian (73%); with average age of 57.5 ± 11 years, 443.1 ± 124 min of nightly PAP use, and 0.97 ± 0.06% of PAP compliance. 73% of patients were male, with no significant differences noted for sleep variables between genders. There was significant decrease in PAP usage duration between pre-DST Mondays and DST Mondays (delta_normalized_PAP_duration = -0.18, p = 0.0027). AHI demonstrated significant decrease on DST Mondays, followed by significant increase on DST Tuesdays (deltaAHI = - 0.54 and 0.47 respectively). This study demonstrated that the effects of DST on duration of PAP use and sleep disruption monitored by AHI are seen days after DST transition, even in the zones with very stable light/dark cycles like Florida, USA.
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Affiliation(s)
- Andreja Packard
- Department of Neurology, Sleep Program, University of Vermont Medical Center, Arnold 2, 2435G 1 South Prospect St, Burlington, VT 05401 India
| | - Jamie S. Amos
- Department of Neurology, University of Florida College of Medicine, Jacksonville, FL USA
| | - Emir Festic
- Center for Sleep Medicine, Mayo Clinic, Jacksonville, FL USA
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2
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Putthanbut N, Su PAB, Lee JY, Borlongan CV. Circadian rhythms in stem cells and their therapeutic potential. Stem Cell Res Ther 2025; 16:85. [PMID: 39988679 PMCID: PMC11849187 DOI: 10.1186/s13287-025-04178-9] [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: 09/03/2024] [Accepted: 01/23/2025] [Indexed: 02/25/2025] Open
Abstract
Circadian rhythms are present in almost all cells, but their existence in stem cells has remains not well established. Circadian clock appears to be closely associated with differentiated mature cells and rarely detected in immature embryonic stem cells. Recent evidence reveals the presence of circadian genes and rhythmic physiologic activities in stem cells as well as stem cell-derived extracellular vesicle (EV) characteristics. The circadian clock entails diverse physiologic and pathological mechanisms underlying cell fate. Integration of circadian rhythm to clinical applications, such as chronotherapy, chrono-biomarker, and environment modification, may facilitate therapeutic outcomes of stem cell-based regenerative medicine. Understanding circadian rhythms in stem cells can optimize stem cell-based therapies by determining the best times for harvesting and administering stem cells, thereby enhancing therapeutic efficacy. Further research into the circadian properties of stem cells will refine stem cell-based therapies, contributing to advancements in regenerative medicine.
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Affiliation(s)
- Napasiri Putthanbut
- Center of Aging and Brain Repair, Department of Neurosurgery, University of South Florida, Tampa, USA
- Department of Medicine, Faculty of Medicine Siriraj Hospital, Mahidol University, Salaya, Thailand
| | - Paul Alexis Bourgade Su
- Center of Aging and Brain Repair, Department of Neurosurgery, University of South Florida, Tampa, USA
- Centro de Investigación en Ciencias de La Salud (CICSA), FCS, Universidad Anáhuac México Campus Norte, Naucalpan, Mexico
| | - Jea-Young Lee
- Center of Aging and Brain Repair, Department of Neurosurgery, University of South Florida, Tampa, USA
| | - Cesario V Borlongan
- Center of Aging and Brain Repair, Department of Neurosurgery, University of South Florida, Tampa, USA.
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3
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Tseng Y. A theoretical systems chronopharmacology approach for COVID-19: Modeling circadian regulation of lung infection and potential precision therapies. CPT Pharmacometrics Syst Pharmacol 2025; 14:340-350. [PMID: 39563101 PMCID: PMC11812942 DOI: 10.1002/psp4.13277] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/23/2024] [Revised: 09/05/2024] [Accepted: 10/30/2024] [Indexed: 11/21/2024] Open
Abstract
The COVID-19 pandemic, caused by SARS-CoV-2, has underscored the urgent need for innovative therapeutic approaches. Recent studies have revealed a complex interplay between the circadian clock and SARS-CoV-2 infection in lung cells, opening new avenues for targeted interventions. This systems pharmacology study investigates this intricate relationship, focusing on the circadian protein BMAL1. BMAL1 plays a dual role in viral dynamics, driving the expression of the viral entry receptor ACE2 while suppressing interferon-stimulated antiviral genes. Its critical position at the host-pathogen interface suggests potential as a therapeutic target, albeit requiring a nuanced approach to avoid disrupting essential circadian regulation. To enable precise tuning of potential interventions, we constructed a computational model integrating the lung cellular clock with viral infection components. We validated this model against literature data to establish a platform for drug administration simulation studies using the REV-ERB agonist SR9009. Our simulations of optimized SR9009 dosing reveal circadian-based strategies that potentially suppress viral infection while minimizing clock disruption. This quantitative framework offers insights into the viral-circadian interface, aiming to guide the development of chronotherapy-based antivirals. More broadly, it underscores the importance of understanding the connections between circadian timing, respiratory viral infections, and therapeutic responses for advancing precision medicine. Such approaches are vital for responding effectively to the rapid spread of coronaviruses like SARS-CoV-2.
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Affiliation(s)
- Yu‐Yao Tseng
- Department of Food Science, Nutrition, and Nutraceutical BiotechnologyShih Chien UniversityTaipeiTaiwan
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4
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Oladapo A, Deshetty UM, Callen S, Buch S, Periyasamy P. Single-Cell RNA-Seq Uncovers Robust Glial Cell Transcriptional Changes in Methamphetamine-Administered Mice. Int J Mol Sci 2025; 26:649. [PMID: 39859365 PMCID: PMC11766323 DOI: 10.3390/ijms26020649] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/15/2024] [Revised: 01/07/2025] [Accepted: 01/12/2025] [Indexed: 01/30/2025] Open
Abstract
Methamphetamine is a highly addictive stimulant known to cause neurotoxicity, cognitive deficits, and immune dysregulation in the brain. Despite significant research, the molecular mechanisms driving methamphetamine-induced neurotoxicity and glial cell dysfunction remain poorly understood. This study investigates how methamphetamine disrupts glial cell function and contributes to neurodevelopmental and neurodegenerative processes. Using single-cell RNA sequencing (scRNA-seq), we analyzed the transcriptomes of 4000 glial cell-associated genes from the cortical regions of mice chronically administered methamphetamine. Methamphetamine exposure altered the key pathways in astrocytes, including the circadian rhythm and cAMP signaling; in microglia, affecting autophagy, ubiquitin-mediated proteolysis, and mitophagy; and in oligodendrocytes, disrupting lysosomal function, cytoskeletal regulation, and protein processing. Notably, several transcription factors, such as Zbtb16, Hif3a, Foxo1, and Klf9, were significantly dysregulated in the glial cells. These findings reveal profound methamphetamine-induced changes in the glial transcriptomes, particularly in the cortical regions, highlighting potential molecular pathways and transcription factors as targets for therapeutic intervention. This study provides novel insights into the glial-mediated mechanisms of methamphetamine toxicity, contributing to our understanding of its effects on the central nervous system and laying the groundwork for future strategies to mitigate its neurotoxic consequences.
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Affiliation(s)
| | | | | | | | - Palsamy Periyasamy
- Department of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center, Omaha, NE 68198, USA; (A.O.); (U.M.D.); (S.C.); (S.B.)
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5
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Carvalho-Moreira JP, de Oliveira Guarnieri L, Passos MC, Emrich F, Bargi-Souza P, Peliciari-Garcia RA, Moraes MFD. CircadiPy: An open-source toolkit for analyzing chronobiology time series. J Neurosci Methods 2024; 411:110245. [PMID: 39117154 DOI: 10.1016/j.jneumeth.2024.110245] [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: 05/07/2024] [Revised: 07/09/2024] [Accepted: 08/05/2024] [Indexed: 08/10/2024]
Abstract
BACKGROUND Chronobiology is the scientific field focused on studying periodicity in biological processes. In mammals, most physiological variables exhibit circadian rhythmicity, such as metabolism, body temperature, locomotor activity, and sleep. The biological rhythmicity can be statistically evaluated by examining the time series and extracting parameters that correlate to the period of oscillation, its amplitude, phase displacement, and overall variability. NEW METHOD We have developed a library called CircadiPy, which encapsulates methods for chronobiological analysis and data inspection, serving as an open-access toolkit for the analysis and interpretation of chronobiological data. The package was designed to be flexible, comprehensive and scalable in order to assist research dealing with processes affected or influenced by rhythmicity. RESULTS The results demonstrate the toolkit's capability to guide users in analyzing chronobiological data collected from various recording sources, while also providing precise parameters related to the circadian rhythmicity. COMPARISON WITH EXISTING METHODS The analysis methodology from this proposed library offers an opportunity to inspect and obtain chronobiological parameters in a straightforward and cost-free manner, in contrast to commercial tools. CONCLUSIONS Moreover, being an open-source tool, it empowers the community with the opportunity to contribute with new functions, analysis methods, and graphical visualizations given the simplified computational method of time series data analysis using an easy and comprehensive pipeline within a single Python object.
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Affiliation(s)
- João Pedro Carvalho-Moreira
- Departamento de Fisiologia e Biofísica, Instituto de Ciências Biológicas - Universidade Federal de Minas Gerais, Belo Horizonte, Brasil; Centro de Tecnologia e Pesquisa em Magneto Ressonância, Programa de Pós-Graduação em Engenharia Elétrica - Universidade Federal de Minas Gerais, Belo Horizonte, Brasil
| | - Leonardo de Oliveira Guarnieri
- Departamento de Fisiologia e Biofísica, Instituto de Ciências Biológicas - Universidade Federal de Minas Gerais, Belo Horizonte, Brasil; Centro de Tecnologia e Pesquisa em Magneto Ressonância, Programa de Pós-Graduação em Engenharia Elétrica - Universidade Federal de Minas Gerais, Belo Horizonte, Brasil
| | - Matheus Costa Passos
- Departamento de Fisiologia e Biofísica, Instituto de Ciências Biológicas - Universidade Federal de Minas Gerais, Belo Horizonte, Brasil
| | - Felipe Emrich
- Departamento de Fisiologia e Biofísica, Instituto de Ciências Biológicas - Universidade Federal de Minas Gerais, Belo Horizonte, Brasil
| | - Paula Bargi-Souza
- Departamento de Fisiologia e Biofísica, Instituto de Ciências Biológicas - Universidade Federal de Minas Gerais, Belo Horizonte, Brasil
| | - Rodrigo Antonio Peliciari-Garcia
- Departamento de Ciências Biológicas, Setor de Morfofisiologia e Patologia, Universidade Federal de São Paulo (UNIFESP), Diadema, SP, Brazil
| | - Márcio Flávio Dutra Moraes
- Departamento de Fisiologia e Biofísica, Instituto de Ciências Biológicas - Universidade Federal de Minas Gerais, Belo Horizonte, Brasil; Centro de Tecnologia e Pesquisa em Magneto Ressonância, Programa de Pós-Graduação em Engenharia Elétrica - Universidade Federal de Minas Gerais, Belo Horizonte, Brasil.
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Bagheri Davisaraei Y, Nateghi S, Rashidipour H, Raise-Abdullahi P, Rashidy-Pour A. Coffee and sleep: Benefits and risks. PROGRESS IN BRAIN RESEARCH 2024; 288:81-114. [PMID: 39168560 DOI: 10.1016/bs.pbr.2024.06.014] [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: 08/23/2024]
Abstract
Consuming coffee, a widely enjoyed beverage with caffeine, can impact the central nervous system and disturb sleep if taken too close to bedtime. Caffeine impacts sleep by slowing the onset, blocking adenosine receptors, lowering deep sleep levels, disrupting sleep patterns, and lessening rapid eye movement sleep. Although coffee can help with alertness in the morning, it may disturb sleep in the evening, particularly for individuals who are sensitive to caffeine. To enhance the quality of sleep, reduce the consumption of caffeine in the afternoon and evening, refrain from drinking caffeine before going to bed, and choose decaffeinated drinks instead. Variables such as personal reactions, ability to handle caffeine, and engagement with other compounds also influence the impact of coffee on sleep. Keeping track of how much caffeine you consume and your sleeping habits can assist in recognizing any disturbances and making needed changes. Furthermore, taking into account variables such as metabolism, age, and the timing of coffee consumption can assist in lessening the effects of coffee on sleep. In general, paying attention to the amount of caffeine consumed from different sources and consuming it at the right times can assist in preserving healthy sleep patterns even while enjoying coffee.
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Affiliation(s)
- Yavar Bagheri Davisaraei
- Research Center of Physiology, Semnan University of Medical Sciences, Semnan, Iran; Department of Physiology, School of Medicine, Semnan University of Medical Sciences, Semnan, Iran
| | - Sepide Nateghi
- Research Center of Physiology, Semnan University of Medical Sciences, Semnan, Iran; Department of Physiology, School of Medicine, Semnan University of Medical Sciences, Semnan, Iran
| | - Hamed Rashidipour
- College of International Education, Dalian Medical University, Dalian, China
| | | | - Ali Rashidy-Pour
- Research Center of Physiology, Semnan University of Medical Sciences, Semnan, Iran; Department of Physiology, School of Medicine, Semnan University of Medical Sciences, Semnan, Iran.
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7
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Bigliardi P, Junnarkar S, Markale C, Lo S, Bigliardi E, Kalyuzhny A, Ong S, Dunn R, Wahli W, Bigliardi-Qi M. The Opioid Receptor Influences Circadian Rhythms in Human Keratinocytes through the β-Arrestin Pathway. Cells 2024; 13:232. [PMID: 38334624 PMCID: PMC10854934 DOI: 10.3390/cells13030232] [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: 11/20/2023] [Revised: 12/21/2023] [Accepted: 01/15/2024] [Indexed: 02/10/2024] Open
Abstract
The recent emphasis on circadian rhythmicity in critical skin cell functions related to homeostasis, regeneration and aging has shed light on the importance of the PER2 circadian clock gene as a vital antitumor gene. Furthermore, delta-opioid receptors (DOPrs) have been identified as playing a crucial role in skin differentiation, proliferation and migration, which are not only essential for wound healing but also contribute to cancer development. In this study, we propose a significant association between cutaneous opioid receptor (OPr) activity and circadian rhythmicity. To investigate this link, we conducted a 48 h circadian rhythm experiment, during which RNA samples were collected every 5 h. We discovered that the activation of DOPr by its endogenous agonist Met-Enkephalin in N/TERT-1 keratinocytes, synchronized by dexamethasone, resulted in a statistically significant 5.6 h delay in the expression of the core clock gene PER2. Confocal microscopy further confirmed the simultaneous nuclear localization of the DOPr-β-arrestin-1 complex. Additionally, DOPr activation not only enhanced but also induced a phase shift in the rhythmic binding of β-arrestin-1 to the PER2 promoter. Furthermore, we observed that β-arrestin-1 regulates the transcription of its target genes, including PER2, by facilitating histone-4 acetylation. Through the ChIP assay, we determined that Met-Enkephalin enhances β-arrestin-1 binding to acetylated H4 in the PER2 promoter. In summary, our findings suggest that DOPr activation leads to a phase shift in PER2 expression via β-arrestin-1-facilitated chromatin remodeling. Consequently, these results indicate that DOPr, much like its role in wound healing, may also play a part in cancer development by influencing PER2.
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Affiliation(s)
- Paul Bigliardi
- Department of Dermatology, University of Minnesota, Minneapolis, MN 55455, USA (C.M.)
- Stem Cell Institue, McGuire Translational Research Facility, University of Minnesota, Minneapolis, MN 55455, USA
| | - Seetanshu Junnarkar
- Agency for Science, Technology and Research, Singapore 138632, Singapore; (S.J.); (S.O.); (R.D.)
| | - Chinmay Markale
- Department of Dermatology, University of Minnesota, Minneapolis, MN 55455, USA (C.M.)
- Stem Cell Institue, McGuire Translational Research Facility, University of Minnesota, Minneapolis, MN 55455, USA
| | - Sydney Lo
- Department of Dermatology, University of Minnesota, Minneapolis, MN 55455, USA (C.M.)
- Stem Cell Institue, McGuire Translational Research Facility, University of Minnesota, Minneapolis, MN 55455, USA
| | - Elena Bigliardi
- Department of Dermatology, University of Minnesota, Minneapolis, MN 55455, USA (C.M.)
- Stem Cell Institue, McGuire Translational Research Facility, University of Minnesota, Minneapolis, MN 55455, USA
| | - Alex Kalyuzhny
- Department of Neuroscience, Medical School, University of Minnesota, Minneapolis, MN 55455, USA;
| | - Sheena Ong
- Agency for Science, Technology and Research, Singapore 138632, Singapore; (S.J.); (S.O.); (R.D.)
| | - Ray Dunn
- Agency for Science, Technology and Research, Singapore 138632, Singapore; (S.J.); (S.O.); (R.D.)
- Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore 639798, Singapore;
| | - Walter Wahli
- Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore 639798, Singapore;
- Unité Mixte de Recherche (UMR) 1331, Institut National de la Recherche Agronomique (INRA), ToxAlim, 31000 Toulouse, France
- Center for Integrative Genomics, University of Lausanne, 1015 Lausanne, Switzerland
| | - Mei Bigliardi-Qi
- Department of Dermatology, University of Minnesota, Minneapolis, MN 55455, USA (C.M.)
- Stem Cell Institue, McGuire Translational Research Facility, University of Minnesota, Minneapolis, MN 55455, USA
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8
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Yang Y, Yuan R, Lu Y, Zhu C, Zhang C, Lue H, Zhang X. The engagement of autophagy in maniac disease. CNS Neurosci Ther 2023; 29:3684-3692. [PMID: 37438945 PMCID: PMC10651947 DOI: 10.1111/cns.14353] [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: 12/17/2022] [Revised: 06/16/2023] [Accepted: 06/30/2023] [Indexed: 07/14/2023] Open
Abstract
AIMS Mania is a prevalent psychiatric disorder with undefined pathological mechanism. Here, we reviewed current knowledge indicating the potential involvement of autophagy dysregulation in mania and further discussed whether targeting autophagy could be a promising strategy for mania therapy. DISCUSSIONS Accumulating evidence indicated the involvement of autophagy in the pathology of mania. One of the most well-accepted mechanisms underlying mania, circadian dysregulation, showed mutual interaction with autophagy dysfunction. In addition, several first-line drugs for mania therapy were found to regulate neuronal autophagy. Besides, deficiencies in mitochondrial quality control, neurotransmission, and ion channel, which showed causal links to mania, were intimately associated with autophagy dysfunction. CONCLUSIONS Although more efforts should be made to either identify the key pathology of mania, the current evidence supported that autophagy dysregulation may act as a possible mechanism involved in the onset of mania-like symptoms. It is therefore a potential strategy to treat manic disorder by correting autophagy.
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Affiliation(s)
- Yidong Yang
- Institute of Pharmacology & Toxicology, College of Pharmaceutical SciencesZhejiang UniversityHangzhouChina
| | - Renxiang Yuan
- Institute of Pharmacology & Toxicology, College of Pharmaceutical SciencesZhejiang UniversityHangzhouChina
| | - Yangyang Lu
- Institute of Pharmacology & Toxicology, College of Pharmaceutical SciencesZhejiang UniversityHangzhouChina
| | - Chenze Zhu
- Institute of Pharmacology & Toxicology, College of Pharmaceutical SciencesZhejiang UniversityHangzhouChina
| | - Chen Zhang
- Institute of Pharmacology & Toxicology, College of Pharmaceutical SciencesZhejiang UniversityHangzhouChina
| | - Haifeng Lue
- School of PharmacyHangzhou Medical CollegeHangzhouChina
| | - Xiangnan Zhang
- Institute of Pharmacology & Toxicology, College of Pharmaceutical SciencesZhejiang UniversityHangzhouChina
- Jinhua Institute of Zhejiang UniversityJinhuaChina
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9
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Peng YF, Wang LL, Gu JH, Zeng YQ. Effects of astaxanthin on depressive and sleep symptoms: A narrative mini-review. Heliyon 2023; 9:e18288. [PMID: 37539097 PMCID: PMC10393630 DOI: 10.1016/j.heliyon.2023.e18288] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/04/2022] [Revised: 07/03/2023] [Accepted: 07/13/2023] [Indexed: 08/05/2023] Open
Abstract
Major depressive disorder (MDD) is a prevalent psychiatric condition that results in persistent feelings of sadness and loss of interest, imposing a significant economic burden on health systems and society. Impaired sleep is both a symptom and a risk factor for depression. Natural astaxanthin (AST), a carotenoid primarily derived from algae and aquatic animals, possesses multiple pharmacological properties such as anti-inflammatory, anti-apoptotic, and antioxidant stress effects. Prior research suggests that AST may have antidepressant properties. This mini-review highlights the potential mechanisms by which AST can prevent depression, providing novel insights into drug research for depression treatment. Specifically, this mechanism suggests that astaxanthin may improve sleep and thus potentially aid in the treatment of depression.
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Affiliation(s)
| | | | | | - Yue-Qin Zeng
- Corresponding author. Academy of Biomedical Engineering, Kunming Medical University, Kunming, China.
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10
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Gupta M, Gupta N, Fradkin Y, Petti T. Sleep Disturbances in Children and Adolescents with Autism
Spectrum Disorder: An Overview for Clinicians. ADOLESCENT PSYCHIATRY 2023; 13:1-24. [DOI: 10.2174/2210676613666230126115646] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/23/2022] [Revised: 09/12/2022] [Accepted: 10/27/2022] [Indexed: 01/28/2023]
Abstract
Background:
Sleep disorders in autism spectrum disorders (ASD/SD) are
distinct, broad, and highly variable clinical entities that ubiquitously affect core
symptomatology, development of comorbid disorders, and overall quality of life for affected
children and families. High genetic predisposition and the presence of co-occurring
disorders present significant challenges in assessment and appropriate interventions.
Objective:
The study aimed to review the best available evidence and address the clinical
gaps in the knowledge about sleep disorders in children and adolescents with autism
spectrum disorders.
Methods:
The review provides a comprehensive literature search of 1622 articles and
summarizes 110 selected for empirical evidence to methodically consider critical aspects of
sleep disorders in ASD for informing clinicians of useful information.
Results:
Clinicians have insufficient guidance and support to effectively manage sleep
disruptions in ASD youth in practice. Prevalence of sleep disruption in ASD, close to 80%, is
characterized by unique subtypes, including but not limited to obstructive sleep apnea,
circadian rhythm disorders, and sleep-related movement disorders. Greater awareness of sleep
disruption, its neurodevelopmental basis, scope, and impact allows for improved treatment and
prevention efforts of these conditions, and is critical for clinical practice and future research.
The bidirectional nature of disruptive sleep and ASD is considered a major area requiring
further clarification.
Conclusion:
Clinician-friendly screening tools are needed for everyday office practice to
identify ASD/SD conditions and interventions, and mitigate harmful effects.
Psychoeducational and cognitive-behavioral approaches for improving and supporting
healthy sleep hygiene, considered the first line of treatment, are detailed. The weak database
for the use of psychopharmacologic agents is summarized, and the strength of prescribing
prolonged-release melatonin for optimal results is described. The promise of other
medications is discussed.
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Affiliation(s)
- Mayank Gupta
- Department of Psychiatry, Clarion Psychiatric Center, Clarion, PA, USA
| | - Nihit Gupta
- Department of Psychiatry,
West Virginia University, Reynolds Memorial Hospital, Glendale, WV, USA
| | - Yuli Fradkin
- Department of
Psychiatry, Rutgers University-Robert Wood Johnson Medical School, Piscataway, NJ, USA
| | - Theodore Petti
- Department of
Psychiatry, Rutgers University-Robert Wood Johnson Medical School, Piscataway, NJ, USA
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11
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Jiang Y, Wang S, Lin W, Gu J, Li G, Shao Y. BMAL1 Promotes Valvular Interstitial Cells’ Osteogenic Differentiation through NF-κ B/AKT/MAPK Pathway. J Cardiovasc Dev Dis 2023; 10:jcdd10030110. [PMID: 36975874 PMCID: PMC10054744 DOI: 10.3390/jcdd10030110] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/03/2023] [Revised: 02/27/2023] [Accepted: 03/01/2023] [Indexed: 03/08/2023] Open
Abstract
Objectives: Calcific aortic valve disease (CAVD) is most common in the aging population and is without effective medical treatments. Brain and muscle ARNT-like 1 (BMAL1) is related to calcification. It has unique tissue-specific characteristics and plays different roles in different tissues’ calcification processes. The purpose of the present study is to explore the role of BMAL1 in CAVD. Methods: The protein levels of BMAL1 in normal and calcified human aortic valves and valvular interstitial cells (VICs) isolated from normal and calcified human aortic valves were checked. HVICs were cultured in osteogenic medium as an in vitro model, and BMAL1 expression and location were detected. TGF-β and RhoA/ROCK inhibitors and RhoA-siRNA were applied to detect the mechanism underlying the source of BMAL1 during HVICs’ osteogenic differentiation. ChIP was applied to check whether BMAL1 could directly interact with the runx2 primer CPG region, and the expression of key proteins involved in the TNF signaling pathway and NF-κ B pathway was tested after silencing BMAL1. Results: In this study, we found that BMAL1 expression was elevated in calcified human aortic valves and VICs isolated from calcified human aortic valves. Osteogenic medium could promote BMAL1 expression in HVICs and the knockdown of BMAL1 induced the inhibition of HVICs’ osteogenic differentiation. Furthermore, the osteogenic medium promoting BMAL1 expression could be blocked by TGF-β and RhoA/ROCK inhibitors and RhoA-siRNA. Meanwhile, BMAL1 could not bind with the runx2 primer CPG region directly, but knockdown of BMAL1 led to decreased levels of P-AKT, P-IκBα, P-p65 and P-JNK. Conclusions: Osteogenic medium could promote BMAL1 expression in HVICs through the TGF-β/RhoA/ROCK pathway. BMAL1 could not act as a transcription factor, but functioned through the NF-κ B/AKT/MAPK pathway to regulate the osteogenic differentiation of HVICs.
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Affiliation(s)
- Yefan Jiang
- Department of Cardiovascular Surgery, The First Affiliated Hospital of Nanjing Medical University, Guangzhou Road, No. 300, Nanjing 210029, China
| | - Song Wang
- Department of Cardiovascular Surgery, The First Affiliated Hospital of Nanjing Medical University, Guangzhou Road, No. 300, Nanjing 210029, China
| | - Wenfeng Lin
- Department of Cardiovascular Surgery, The First Affiliated Hospital of Nanjing Medical University, Guangzhou Road, No. 300, Nanjing 210029, China
| | - Jiaxi Gu
- Department of Cardiovascular Surgery, The First Affiliated Hospital of Nanjing Medical University, Guangzhou Road, No. 300, Nanjing 210029, China
| | - Geng Li
- Department of Cardiovascular Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Jiefang Road, No. 1277, Wuhan 430022, China
- Correspondence: (G.L.); (Y.S.); Tel.: +86-027-85351611 (G.L.); +86-025-68303574 (Y.S.)
| | - Yongfeng Shao
- Department of Cardiovascular Surgery, The First Affiliated Hospital of Nanjing Medical University, Guangzhou Road, No. 300, Nanjing 210029, China
- Correspondence: (G.L.); (Y.S.); Tel.: +86-027-85351611 (G.L.); +86-025-68303574 (Y.S.)
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Kalita E, Panda M, Prajapati VK. The interplay between circadian clock and viral infections: A molecular perspective. ADVANCES IN PROTEIN CHEMISTRY AND STRUCTURAL BIOLOGY 2023; 137:293-330. [PMID: 37709380 DOI: 10.1016/bs.apcsb.2023.02.009] [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: 09/16/2023]
Abstract
The circadian clock influences almost every aspect of mammalian behavioral, physiological and metabolic processes. Being a hierarchical network, the circadian clock is driven by the central clock in the brain and is composed of several peripheral tissue-specific clocks. It orchestrates and synchronizes the daily oscillations of biological processes to the environment. Several pathological events are influenced by time and seasonal variations and as such implicate the clock in pathogenesis mechanisms. In context with viral infections, circadian rhythmicity is closely associated with host susceptibility, disease severity, and pharmacokinetics and efficacies of antivirals and vaccines. Leveraging the circadian molecular mechanism insights has increased our understanding of clock infection biology and proposes new avenues for viral diagnostics and therapeutics. In this chapter, we address the molecular interplay between the circadian clock and viral infections and discuss the importance of chronotherapy as a complementary approach to conventional medicines, emphasizing the significance of virus-clock studies.
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Affiliation(s)
- Elora Kalita
- Department of Biochemistry, School of Life Sciences, Central University of Rajasthan, Ajmer, Rajasthan, India
| | - Mamta Panda
- Department of Biochemistry, School of Life Sciences, Central University of Rajasthan, Ajmer, Rajasthan, India
| | - Vijay Kumar Prajapati
- Department of Biochemistry, University of Delhi South Campus, Benito Juarez Road, Dhaula Kuan, New Delhi, India..
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Zhang H, Shan G, Jin X, Yu X, Bi G, Feng M, Wang H, Lin M, Zhan C, Wang Q, Li M. ARNTL2 is an indicator of poor prognosis, promotes epithelial-to-mesenchymal transition and inhibits ferroptosis in lung adenocarcinoma. Transl Oncol 2022; 26:101562. [PMID: 36228410 PMCID: PMC9563212 DOI: 10.1016/j.tranon.2022.101562] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/15/2022] [Revised: 09/17/2022] [Accepted: 10/05/2022] [Indexed: 11/21/2022] Open
Abstract
OBJECTIVES ARNTL2, as a circadian transcription factor, has been recently proposed to play an important role in a variety of tumors. however, the role of ARNTL2 in lung carcinogenesis and progression remains unclear. The purpose of this study was to investigate the effect of ARNTL2 on the clinical characteristics and prognosis of lung adenocarcinoma and to explore the relationship between ARNTL2 and EMT, ferroptosis in lung adenocarcinoma. METHODS The Cancer Genome Atlas (TCGA) database's multi-omics data were downloaded using the Xena browser. Based on the expression levels of ARNTL2, patients with lung adenocarcinoma from TCGA were divided into two groups: those with high ARNTL2 expression and those with low ARNTL2 expression. ARNTL2 was studied for its effects on lung adenocarcinoma's clinicopathological, genomic, and immunological characteristics. Furthermore, in vivo and in vitro assays were used to confirm the impact of ARNLT2 knockdown on lung adenocarcinoma cells. RESULTS We found ARNTL2 is highly expressed in lung adenocarcinoma and was an independent predictor of a poor prognosis in patients with lung adenocarcinoma. In addition, we demonstrated that knockdown of ARNTL2 promoted ferroptosis, inhibited EMT, cell proliferation, migration and invasion in lung adenocarcinoma. In contrast, overexpressing ARNTL2 yielded the opposite results. CONCLUSIONS ARNTL2 is an independent unfavorable prognostic factor for lung adenocarcinoma. It plays a facilitating role in the development of lung adenocarcinoma, especially in promoting EMT and inhibiting ferroptosis, revealing that ARNTL2 may be a potential biomarker for lung adenocarcinoma.
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Affiliation(s)
- Huan Zhang
- Department of Thoracic Surgery, Zhongshan Hospital, Fudan University, Shanghai, China; Cancer Center, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Guangyao Shan
- Department of Thoracic Surgery, Zhongshan Hospital, Fudan University, Shanghai, China; Cancer Center, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Xing Jin
- Department of Thoracic Surgery, Zhongshan Hospital, Fudan University, Shanghai, China; Cancer Center, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Xiangyang Yu
- Department of Thoracic Surgery, Peking Union Medical College, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital/Shenzhen Hospital, Chinese Academy of Medical Sciences, Shenzhen, China
| | - GuoShu Bi
- Department of Thoracic Surgery, Zhongshan Hospital, Fudan University, Shanghai, China; Cancer Center, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Mingxiang Feng
- Department of Thoracic Surgery, Zhongshan Hospital, Fudan University, Shanghai, China; Cancer Center, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Hao Wang
- Department of Thoracic Surgery, Zhongshan Hospital, Fudan University, Shanghai, China; Cancer Center, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Miao Lin
- Department of Thoracic Surgery, Zhongshan Hospital, Fudan University, Shanghai, China; Cancer Center, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Cheng Zhan
- Department of Thoracic Surgery, Zhongshan Hospital, Fudan University, Shanghai, China; Cancer Center, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Qun Wang
- Department of Thoracic Surgery, Zhongshan Hospital, Fudan University, Shanghai, China; Cancer Center, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Ming Li
- Department of Thoracic Surgery, Zhongshan Hospital, Fudan University, Shanghai, China; Cancer Center, Zhongshan Hospital, Fudan University, Shanghai, China.
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Putilov A. Prospects of Testing Diurnal Profiles of Expressions of TSH-R and Circadian Clock Genes in Thyrocytes for Identification of Preoperative Biomarkers for Thyroid Carcinoma. Int J Mol Sci 2022; 23:12208. [PMID: 36293065 PMCID: PMC9603503 DOI: 10.3390/ijms232012208] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/21/2022] [Revised: 10/04/2022] [Accepted: 10/11/2022] [Indexed: 11/17/2022] Open
Abstract
Thyroid Nodules (TN) are frequent but mostly benign, and postoperative rate of benign TN attains the values from 70% to 90%. Therefore, there is an urgent need for identification of reliable preoperative diagnosis markers for patients with indeterminate thyroid cytology. In this study, an earlier unexplored design of research on preoperative biomarkers for thyroid malignancies was proposed. Evaluation of reported results of studies addressing the links of thyroid cancer to the circadian clockwork dysfunctions and abnormal activities of Thyroid-Stimulating Hormone (TSH) and its receptor (TSH-R) suggested diagnostic significance of such links. However, there is still a gap in studies of interrelationships between diurnal profiles of expression of circadian clock genes and TSH-R in indeterminate thyroid tissue exposed to different concentrations of TSH. These interrelationships might be investigated in future in vitro experiments on benign and malignant thyrocytes cultivated under normal and challenged TSH levels. Their design requires simultaneous measurement of diurnal profiles of expression of both circadian clock genes and TSH-R. Experimental results might help to bridge previous studies of preoperative biomarkers for thyroid carcinoma exploring diagnostic value of diurnal profiles of serum TSH levels, expression of TSH-R, and expression of circadian clock genes.
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Affiliation(s)
- Arcady Putilov
- Research Group for Math-Modeling of Biomedical Systems, Research Institute for Molecular Biology and Biophysics of the Federal Research Centre for Fundamental and Translational Medicine, 630117 Novosibirsk, Russia; ; Tel.: +49-30-53674643 or +49-30-61290031
- Laboratory of Sleep/Wake Neurobiology, Institute of Higher Nervous Activity and Neurophysiology of the Russian Academy of Sciences, 117865 Moscow, Russia
- Laboratory of Nanobiotechnology and Biophysics, North-Caucasus Federal University, 355029 Stavropol, Russia
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15
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Bilu C, Einat H, Zimmet P, Kronfeld-Schor N. Circadian rhythms-related disorders in diurnal fat sand rats under modern lifestyle conditions: A review. Front Physiol 2022; 13:963449. [PMID: 36160856 PMCID: PMC9489903 DOI: 10.3389/fphys.2022.963449] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/07/2022] [Accepted: 08/11/2022] [Indexed: 11/17/2022] Open
Abstract
Modern lifestyle reduces environmental rhythmicity and may lead to circadian desynchrony. We are exposed to poor day-time lighting indoors and excessive night-time artificial light. We use air-conditioning to reduce ambient temperature cycle, and food is regularly available at all times. These disruptions of daily rhythms may lead to type 2 diabetes mellitus (T2DM), obesity, cardiometabolic diseases (CMD), depression and anxiety, all of which impose major public health and economic burden on societies. Therefore, we need appropriate animal models to gain a better understanding of their etiologic mechanisms, prevention, and management.We argue that the fat sand rat (Psammomys obesus), a diurnal animal model, is most suitable for studying the effects of modern-life conditions. Numerous attributes make it an excellent model to study human health disorders including T2DM, CMD, depression and anxiety. Here we review a comprehensive series of studies we and others conducted, utilizing the fat sand rat to study the underlying interactions between biological rhythms and health. Understanding these interactions will help deciphering the biological basis of these diseases, which often occur concurrently. We found that when kept in the laboratory (compared with natural and semi-wild outdoors conditions where they are diurnal), fat sand rats show low amplitude, nocturnal or arrhythmic activity patterns, dampened daily glucose rhythm, glucose intolerance, obesity and decreased survival rates. Short photoperiod acclimation exacerbates these pathologies and further dampens behavioral and molecular daily rhythms, resulting in CMD, T2DM, obesity, adipocyte dysfunction, cataracts, depression and anxiety. Increasing environmental rhythmicity by morning bright light exposure or by access to running wheels strengthens daily rhythms, and results in higher peak-to-trough difference in activity, better rhythmicity in clock genes expression, lower blood glucose and insulin levels, improved glucose tolerance, lower body and heart weight, and lower anxiety and depression. In summary, we have demonstrated that fat sand rats living under the correspondent of “human modern lifestyle” conditions exhibit dampened behavioral and biological rhythms and develop circadian desynchrony, which leads to what we have named “The Circadian Syndrome”. Environmental manipulations that increase rhythmicity result in improvement or prevention of these pathologies. Similar interventions in human subjects could have the same positive results and further research on this should be undertaken.
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Affiliation(s)
- Carmel Bilu
- School of Zoology, Tel-Aviv University, Tel Aviv, Israel
- *Correspondence: Carmel Bilu,
| | - Haim Einat
- School of Behavioral Sciences, Tel Aviv-Yaffo Academic College, Tel-Aviv, Israel
| | - Paul Zimmet
- Department of Diabetes, Monash University, Melbourne, VIC, Australia
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16
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Dardente H, Simonneaux V. GnRH and the photoperiodic control of seasonal reproduction: Delegating the task to kisspeptin and RFRP-3. J Neuroendocrinol 2022; 34:e13124. [PMID: 35384117 DOI: 10.1111/jne.13124] [Citation(s) in RCA: 22] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/01/2021] [Revised: 02/22/2022] [Accepted: 03/03/2022] [Indexed: 10/18/2022]
Abstract
Synchronization of mammalian breeding activity to the annual change of photoperiod and environmental conditions is of the utmost importance for individual survival and species perpetuation. Subsequent to the early 1960s, when the central role of melatonin in this adaptive process was demonstrated, our comprehension of the mechanisms through which light regulates gonadal activity has increased considerably. The current model for the photoperiodic neuroendocrine system points to pivotal roles for the melatonin-sensitive pars tuberalis (PT) and its seasonally-regulated production of thyroid-stimulating hormone (TSH), as well as for TSH-sensitive hypothalamic tanycytes, radial glia-like cells located in the basal part of the third ventricle. Tanycytes respond to TSH through increased expression of thyroid hormone (TH) deiodinase 2 (Dio2), which leads to heightened production of intrahypothalamic triiodothyronine (T3) during longer days of spring and summer. There is strong evidence that this local, long-day driven, increase in T3 links melatonin input at the PT to gonadotropin-releasing hormone (GnRH) output, to align breeding with the seasons. The mechanism(s) through which T3 impinges upon GnRH remain(s) unclear. However, two distinct neuronal populations of the medio-basal hypothalamus, which express the (Arg)(Phe)-amide peptides kisspeptin and RFamide-related peptide-3, appear to be well-positioned to relay this seasonal T3 message towards GnRH neurons. Here, we summarize our current understanding of the cellular, molecular and neuroendocrine players, which keep track of photoperiod and ultimately govern GnRH output and seasonal breeding.
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Affiliation(s)
- Hugues Dardente
- CNRS, IFCE, INRAE, Université de Tours, PRC, Nouzilly, France
| | - Valérie Simonneaux
- Institute for Cellular and Integrative Neuroscience, University of Strasbourg, Strasbourg, France
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17
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Ionadi A, Johnson JD. Interaction between corticosterone and PER2 in regulating emotional behaviors in the rat. Psychoneuroendocrinology 2022; 137:105628. [PMID: 34952453 DOI: 10.1016/j.psyneuen.2021.105628] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/02/2021] [Revised: 10/27/2021] [Accepted: 12/10/2021] [Indexed: 11/30/2022]
Abstract
Circadian rhythms play a prominent role in psychiatric health with disruption in rhythms associated with poor mental health. Corticosterone (CORT) is an important hormone in entraining the biological rhythms of many cells throughout the body and coordinating peripheral rhythms with the central master clock. Here, we tested the hypothesis that excess CORT during the circadian trough would lead to a flattening of period genes (Per1 and Per2) rhythms in limbic brain areas, and thus impact emotional behaviors. Male rats were injected daily with 2.5 mg/kg CORT or vehicle for 21 days at either ZT0 or ZT12 and sucrose preference, open field, and forced swim behaviors measured during the dark phase of the light cycle. After three weeks of injections, a reduction in sucrose preference was observed in animals injected with CORT at ZT0 and the reduction significantly correlated with reductions in Per2 mRNA expression in the central amygdala (CeA) and bed nucleus of the stria terminalis (BNST). No changes in behavior or period gene expression were observed in animals injected with CORT at ZT12. DsiRNA was used to directly reduce Per2 levels in either the CeA or BNST and behavior was assessed. Despite reductions in Per2 expression in the CeA, no behavioral changes were observed. In contrast, a reduction in Per2 expression in the BNST was sufficient to reduce sucrose preference. The results demonstrate that CORT significantly contributes to the circadian expression of Period genes in certain limbic brain areas and disruption in diurnal CORT or Per2 expression can lead to impaired emotional behavioral responses.
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Affiliation(s)
- Amy Ionadi
- Kent State University, School of Biomedical Sciences, Kent, OH 44240, United States
| | - John D Johnson
- Kent State University, School of Biomedical Sciences, Kent, OH 44240, United States; Kent State University, Biological Sciences Department, Kent, OH 44240, United States; Kent State University, Brain Health Research Institute, Kent, OH 44242, United States.
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Abstract
Endogenous biological clocks, orchestrated by the suprachiasmatic nucleus, time the circadian rhythms that synchronize physiological and behavioural functions in humans. The circadian system influences most physiological processes, including sleep, alertness and cognitive performance. Disruption of circadian homeostasis has deleterious effects on human health. Neurodegenerative disorders involve a wide range of symptoms, many of which exhibit diurnal variations in frequency and intensity. These disorders also disrupt circadian homeostasis, which in turn has negative effects on symptoms and quality of life. Emerging evidence points to a bidirectional relationship between circadian homeostasis and neurodegeneration, suggesting that circadian function might have an important role in the progression of neurodegenerative disorders. Therefore, the circadian system has become an attractive target for research and clinical care innovations. Studying circadian disruption in neurodegenerative disorders could expand our understanding of the pathophysiology of neurodegeneration and facilitate the development of novel, circadian-based interventions for these disabling disorders. In this Review, we discuss the alterations to the circadian system that occur in movement (Parkinson disease and Huntington disease) and cognitive (Alzheimer disease and frontotemporal dementia) neurodegenerative disorders and provide directions for future investigations in this field.
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19
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Feng C, Liu W, Chen H, Dong W, Yang J. Effect of dark environment on intestinal flora and expression of genes related to liver metabolism in zebrafish (Danio rerio). Comp Biochem Physiol C Toxicol Pharmacol 2021; 249:109100. [PMID: 34174412 DOI: 10.1016/j.cbpc.2021.109100] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/24/2021] [Revised: 05/19/2021] [Accepted: 05/26/2021] [Indexed: 02/07/2023]
Abstract
To explore the effects of dark environment on intestinal flora and expression of genes related to liver metabolism in zebrafish, a total of 60 zebrafish were fed for 21 days (24 h dark treatments or 14/10 h light/dark cycle), and the influence of dark environment on gut microbes and liver gene expression was studied using sequencing analysis of intestinal flora and liver. The results showed that the body weight of fish was significantly increased in the dark group than that in the control group (P < 0.05). Compared with the control group, dark environment treatment changed the composition of dominant flora, increased the abundance of unconventional bacteria and reduced probiotics in the intestine of zebrafish. Of these, the ratio of Bacteroidetes to Firmicutes in the intestine was reduced. The genome expression of the liver showed significant changes, and liver metabolites were also affected. Meanwhile, dark environment decreased gene expression associated with changes in blood glucose, lipid metabolism and immunization. Dark environment also caused liver steatosis as observed by histological study. This study shows that dark environment treatment has an important impact on liver metabolism and intestinal microbes in zebrafish.
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Affiliation(s)
- Chi Feng
- Inner Mongolia Key Laboratory of Toxicant Monitoring and Toxicology, College of Animal Science and Technology, Inner Mongolia University for Nationalities, Tongliao, Inner Mongolia 028000, China
| | - Wuyun Liu
- Inner Mongolia Key Laboratory of Toxicant Monitoring and Toxicology, College of Animal Science and Technology, Inner Mongolia University for Nationalities, Tongliao, Inner Mongolia 028000, China; School of Animal Science, Mongolian State University of Agriculture, Bayangol, Ulaanbaatar, Mongolia
| | - Hao Chen
- Inner Mongolia Key Laboratory of Toxicant Monitoring and Toxicology, College of Animal Science and Technology, Inner Mongolia University for Nationalities, Tongliao, Inner Mongolia 028000, China
| | - Wu Dong
- Inner Mongolia Key Laboratory of Toxicant Monitoring and Toxicology, College of Animal Science and Technology, Inner Mongolia University for Nationalities, Tongliao, Inner Mongolia 028000, China
| | - Jingfeng Yang
- Inner Mongolia Key Laboratory of Toxicant Monitoring and Toxicology, College of Animal Science and Technology, Inner Mongolia University for Nationalities, Tongliao, Inner Mongolia 028000, China.
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20
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Knoedler JR, Sáenz de Miera C, Subramani A, Denver RJ. An Intact Krüppel-like factor 9 Gene Is Required for Acute Liver Period 1 mRNA Response to Restraint Stress. Endocrinology 2021; 162:6255381. [PMID: 33904929 PMCID: PMC8312639 DOI: 10.1210/endocr/bqab083] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/16/2021] [Indexed: 12/14/2022]
Abstract
The clock protein period 1 (PER1) is a central component of the core transcription-translation feedback loop governing cell-autonomous circadian rhythms in animals. Transcription of Per1 is directly regulated by the glucocorticoid (GC) receptor (GR), and Per1 mRNA is induced by stressors or injection of GC. Circulating GCs may synchronize peripheral clocks with the central pacemaker located in the suprachiasmatic nucleus of the brain. Krüppel-like factor 9 (KLF9) is a zinc finger transcription factor that, like Per1, is directly regulated by liganded GR, and it associates in chromatin at clock and clock-output genes, including at Per1. We hypothesized that KLF9 modulates stressor-dependent Per1 transcription. We exposed wild-type (WT) and Klf9 null mice (Klf9-/-) of both sexes to 1 hour restraint stress, which caused similar 2- to 2.5-fold increases in plasma corticosterone (B) in each genotype and sex. Although WT mice of both sexes showed a 2-fold increase in liver Per1 mRNA level after restraint stress, this response was absent in Klf9-/- mice. However, injection of B in WT and Klf9-/- mice induced similar increases in Per1 mRNA. Our findings support that an intact Klf9 gene is required for liver Per1 mRNA responses to an acute stressor, but a possible role for GCs in this response requires further investigation.
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Affiliation(s)
- Joseph R Knoedler
- Neuroscience Graduate Program, University of Michigan, Ann Arbor, Michigan 48109-2215, USA
- Current Affiliation: J. R. Knoedler’s current affiliation is the Department of Psychiatry and Behavioral Sciences, Stanford University, Stanford, CA 94305, USA
| | - Cristina Sáenz de Miera
- Department of Molecular, Cellular and Developmental Biology, University of Michigan, Ann Arbor, Michigan 48109-1085, USA
- Current Affiliation: C. Sáenz de Miera’s current affiliation is the Department of Molecular and Integrative Physiology, University of Michigan Medical School, Ann Arbor, MI 48109-2800, USA
| | - Arasakumar Subramani
- Department of Molecular, Cellular and Developmental Biology, University of Michigan, Ann Arbor, Michigan 48109-1085, USA
| | - Robert J Denver
- Neuroscience Graduate Program, University of Michigan, Ann Arbor, Michigan 48109-2215, USA
- Department of Molecular, Cellular and Developmental Biology, University of Michigan, Ann Arbor, Michigan 48109-1085, USA
- Correspondence: Robert J. Denver, PhD, Department of Molecular, Cellular and Developmental Biology, 1105 North University Avenue, University of Michigan, Ann Arbor, MI 48109-1085, USA.
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21
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Liu Y, Niu L, Liu X, Cheng C, Le W. Recent Progress in Non-motor Features of Parkinson's Disease with a Focus on Circadian Rhythm Dysregulation. Neurosci Bull 2021; 37:1010-1024. [PMID: 34128188 DOI: 10.1007/s12264-021-00711-x] [Citation(s) in RCA: 25] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/25/2020] [Accepted: 03/31/2021] [Indexed: 12/14/2022] Open
Abstract
Parkinson's disease (PD) is the second most common neurodegenerative disease, which manifests with both motor and non-motor symptoms. Circadian rhythm dysregulation, as one of the most challenging non-motor features of PD, usually appears long before obvious motor symptoms. Moreover, the dysregulated circadian rhythm has recently been reported to play pivotal roles in PD pathogenesis, and it has emerged as a hot topic in PD research. In this review, we briefly introduce the circadian rhythm and circadian rhythm-related genes, and then summarize recent research progress on the altered circadian rhythm in PD, ranging from clinical features to the possible causes of PD-related circadian disorders. We believe that future comprehensive studies on the topic may not only help us to explore the mechanisms of PD, but also shed light on the better management of PD.
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Affiliation(s)
- Yufei Liu
- Liaoning Provincial Key Laboratory for Research on the Pathogenic Mechanisms of Neurological Diseases, the First Affiliated Hospital, Dalian Medical University, Dalian, 116021, China
- Liaoning Provincial Center for Clinical Research on Neurological Diseases, the First Affiliated Hospital, Dalian Medical University, Dalian, 116021, China
| | - Long Niu
- Liaoning Provincial Key Laboratory for Research on the Pathogenic Mechanisms of Neurological Diseases, the First Affiliated Hospital, Dalian Medical University, Dalian, 116021, China
- Liaoning Provincial Center for Clinical Research on Neurological Diseases, the First Affiliated Hospital, Dalian Medical University, Dalian, 116021, China
| | - Xinyao Liu
- Liaoning Provincial Key Laboratory for Research on the Pathogenic Mechanisms of Neurological Diseases, the First Affiliated Hospital, Dalian Medical University, Dalian, 116021, China
- Liaoning Provincial Center for Clinical Research on Neurological Diseases, the First Affiliated Hospital, Dalian Medical University, Dalian, 116021, China
| | - Cheng Cheng
- Liaoning Provincial Key Laboratory for Research on the Pathogenic Mechanisms of Neurological Diseases, the First Affiliated Hospital, Dalian Medical University, Dalian, 116021, China
- Liaoning Provincial Center for Clinical Research on Neurological Diseases, the First Affiliated Hospital, Dalian Medical University, Dalian, 116021, China
| | - Weidong Le
- Liaoning Provincial Key Laboratory for Research on the Pathogenic Mechanisms of Neurological Diseases, the First Affiliated Hospital, Dalian Medical University, Dalian, 116021, China.
- Liaoning Provincial Center for Clinical Research on Neurological Diseases, the First Affiliated Hospital, Dalian Medical University, Dalian, 116021, China.
- Institute of Neurology, Sichuan Academy of Medical Science-Sichuan Provincial Hospital, University of Electronic Science and Technology of China, Chengdu, 610072, China.
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22
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Mondal G, Dharmajyoti Devi S, Khan ZA, Yumnamcha T, Rajiv C, Sanjita Devi H, Chattoraj A. The influence of feeding on the daily rhythm of mRNA expression on melatonin bio-synthesizing enzyme genes and clock associated genes in the zebrafish (Danio rerio) gut. BIOL RHYTHM RES 2021. [DOI: 10.1080/09291016.2021.1905989] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/21/2022]
Affiliation(s)
- Gopinath Mondal
- Biological Rhythm Laboratory, Animal Resources Programme, Department of Biotechnology, Institute of Bioresources and Sustainable Development, Government of India, Imphal, India
- Department of Biotechnology, Gauhati University, Guwahati 781014, Assam, India
| | - Sijagurumayum Dharmajyoti Devi
- Biological Rhythm Laboratory, Animal Resources Programme, Department of Biotechnology, Institute of Bioresources and Sustainable Development, Government of India, Imphal, India
| | - Zeeshan Ahmad Khan
- Biological Rhythm Laboratory, Animal Resources Programme, Department of Biotechnology, Institute of Bioresources and Sustainable Development, Government of India, Imphal, India
| | - Thangal Yumnamcha
- Biological Rhythm Laboratory, Animal Resources Programme, Department of Biotechnology, Institute of Bioresources and Sustainable Development, Government of India, Imphal, India
| | - Chongtham Rajiv
- Biological Rhythm Laboratory, Animal Resources Programme, Department of Biotechnology, Institute of Bioresources and Sustainable Development, Government of India, Imphal, India
| | - Haobijam Sanjita Devi
- Biological Rhythm Laboratory, Animal Resources Programme, Department of Biotechnology, Institute of Bioresources and Sustainable Development, Government of India, Imphal, India
| | - Asamanja Chattoraj
- Biological Rhythm Laboratory, Department of Animal Science, Kazi Nazrul University, Asansol, India
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Dardente H, Migaud M. Thyroid hormone and hypothalamic stem cells in seasonal functions. VITAMINS AND HORMONES 2021; 116:91-131. [PMID: 33752829 DOI: 10.1016/bs.vh.2021.02.005] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
Seasonal rhythms are a pervasive feature of most living organisms, which underlie yearly timeliness in breeding, migration, hibernation or weight gain and loss. To achieve this, organisms have developed inner timing devices (circannual clocks) that endow them with the ability to predict then anticipate changes to come, usually using daylength as the proximate cue. In Vertebrates, daylength interpretation involves photoperiodic control of TSH production by the pars tuberalis (PT) of the pituitary, which governs a seasonal switch in thyroid hormone (TH) availability in the neighboring hypothalamus. Tanycytes, specialized glial cells lining the third ventricle (3V), are responsible for this TH output through the opposite, PT-TSH-driven, seasonal control of deiodinases 2/3 (Dio 2/3). Tanycytes comprise a photoperiod-sensitive stem cell niche and TH is known to play major roles in cell proliferation and differentiation, which suggests that seasonal control of tanycyte proliferation may be involved in the photoperiodic synchronization of seasonal rhythms. Here we review our current knowledge of the molecular and neuroendocrine pathway linking photoperiodic information to seasonal changes in physiological functions and discuss the potential implication of tanycytes, TH and cell proliferation in seasonal timing.
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Affiliation(s)
- Hugues Dardente
- PRC, INRAE, CNRS, IFCE, Université de Tours, Nouzilly, France.
| | - Martine Migaud
- PRC, INRAE, CNRS, IFCE, Université de Tours, Nouzilly, France
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Park S, Park JH, Kang UB, Choi SK, Elfadl A, Ullah HMA, Chung MJ, Son JY, Yun HH, Park JM, Yim JH, Jung SJ, Kim SH, Choi YC, Kim DS, Shin JH, Park JS, Hur K, Lee SH, Lee EJ, Hwang D, Jeong KS. Nogo-A regulates myogenesis via interacting with Filamin-C. Cell Death Discov 2021; 7:1. [PMID: 33414425 PMCID: PMC7791112 DOI: 10.1038/s41420-020-00384-x] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/02/2020] [Revised: 11/22/2020] [Accepted: 11/28/2020] [Indexed: 12/23/2022] Open
Abstract
Among the three isoforms encoded by Rtn4, Nogo-A has been intensely investigated as a central nervous system inhibitor. Although Nogo-A expression is increased in muscles of patients with amyotrophic lateral sclerosis, its role in muscle homeostasis and regeneration is not well elucidated. In this study, we discovered a significant increase in Nogo-A expression in various muscle-related pathological conditions. Nogo−/− mice displayed dystrophic muscle structure, dysregulated muscle regeneration following injury, and altered gene expression involving lipid storage and muscle cell differentiation. We hypothesized that increased Nogo-A levels might regulate muscle regeneration. Differentiating myoblasts exhibited Nogo-A upregulation and silencing Nogo-A abrogated myoblast differentiation. Nogo-A interacted with filamin-C, suggesting a role for Nogo-A in cytoskeletal arrangement during myogenesis. In conclusion, Nogo-A maintains muscle homeostasis and integrity, and pathologically altered Nogo-A expression mediates muscle regeneration, suggesting Nogo-A as a novel target for the treatment of myopathies in clinical settings.
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Affiliation(s)
- SunYoung Park
- Department of Pathology, College of Veterinary Medicine, Kyungpook National University, Daegu, 41566, Republic of Korea.,Stem Cell Therapeutic Research Institute, Kyungpook National University, Daegu, 41566, Republic of Korea
| | - Ji-Hwan Park
- Department of New Biology, DGIST, Daegu, 42988, Republic of Korea
| | - Un-Beom Kang
- R&D Division, BERTIS, Inc., Seongnam-si, Gyeonggi-do, 13605, Republic of Korea
| | - Seong-Kyoon Choi
- Division of Biotechnology, DGIST, Daegu, 42988, Republic of Korea.,Core Protein Resources Center, DGIST, Daegu, 42988, Republic of Korea
| | - Ahmed Elfadl
- Department of Pathology, College of Veterinary Medicine, Kyungpook National University, Daegu, 41566, Republic of Korea
| | - H M Arif Ullah
- Department of Pathology, College of Veterinary Medicine, Kyungpook National University, Daegu, 41566, Republic of Korea
| | - Myung-Jin Chung
- Department of Pathology, College of Veterinary Medicine, Kyungpook National University, Daegu, 41566, Republic of Korea
| | - Ji-Yoon Son
- Department of Pathology, College of Veterinary Medicine, Kyungpook National University, Daegu, 41566, Republic of Korea
| | - Hyun Ho Yun
- Department of Pathology, College of Veterinary Medicine, Kyungpook National University, Daegu, 41566, Republic of Korea
| | - Jae-Min Park
- Department of Pathology, College of Veterinary Medicine, Kyungpook National University, Daegu, 41566, Republic of Korea
| | - Jae-Hyuk Yim
- Department of Pathology, College of Veterinary Medicine, Kyungpook National University, Daegu, 41566, Republic of Korea
| | - Seung-Jun Jung
- Department of Pathology, College of Veterinary Medicine, Kyungpook National University, Daegu, 41566, Republic of Korea
| | - Sang-Hyup Kim
- Department of Pathology, College of Veterinary Medicine, Kyungpook National University, Daegu, 41566, Republic of Korea
| | - Young-Chul Choi
- Department of Neurology, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, 06058, Republic of Korea
| | - Dae-Seong Kim
- Department of Neurology, Pusan National University Yangsan Hospital, Yangsan, 50612, Republic of Korea
| | - Jin-Hong Shin
- Department of Neurology, Pusan National University Yangsan Hospital, Yangsan, 50612, Republic of Korea
| | - Jin-Sung Park
- Department of Neurology, Kyungpook National University School of Medicine, Daegu, 41944, Republic of Korea
| | - Keun Hur
- Department of Biochemistry and Cell Biology, Kyungpook National University School of Medicine, Daegu, 41944, Republic of Korea
| | - Sang-Han Lee
- Department of Food Science and Biotechnology, Kyungpook National University, Daegu, 41566, Republic of Korea
| | - Eun-Joo Lee
- Department of Pathology, College of Veterinary Medicine, Kyungpook National University, Daegu, 41566, Republic of Korea
| | - Daehee Hwang
- Department of Biological Sciences, Seoul National University, Seoul, 08826, Republic of Korea
| | - Kyu-Shik Jeong
- Department of Pathology, College of Veterinary Medicine, Kyungpook National University, Daegu, 41566, Republic of Korea. .,Stem Cell Therapeutic Research Institute, Kyungpook National University, Daegu, 41566, Republic of Korea.
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25
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Vasopressin in circadian function of SCN. J Biosci 2020. [DOI: 10.1007/s12038-020-00109-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/23/2022]
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26
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Abstract
The ability of organisms to keep track of external time, by means of the circadian clock interacting with the environment, is essential for health. The focus of this review is recent methods to detect the internal circadian time of an omics sample. Before reaching our main topic, we introduce the circadian clock, its hierarchical structure, and its main functions; we will also explain the notion of internal time, or circadian phase, and how it differs from the geophysical time. We then focus on the role played by the clock in the maintenance of human heath, in particular in the context of cancer. Thereafter, we analyze an important methodological question: how to infer the circadian phase of unlabeled omics snapshot measurements. Answering this question could both significantly increase our understanding of the circadian clock and allow the use of this knowledge in biomedical applications. We review existing methods, focusing on the more recent ones, following a historical trajectory. We explain the basic concepts underlying the methods, as well as some crucial technical aspects of each. We conclude by reporting how some of these methods have, more or less effectively, enabled furthering our understanding of the clock and given insights regarding potential biomedical applications.
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Affiliation(s)
- Lorenzo Talamanca
- The Institute of Bioengineering (IBI), School of Life Science, Ecole Polytechnique Fédérale de Lausanne (EPFL), Lausanne, Switzerland
| | - Felix Naef
- The Institute of Bioengineering (IBI), School of Life Science, Ecole Polytechnique Fédérale de Lausanne (EPFL), Lausanne, Switzerland
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27
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Luo Y, Yang J, Kang J, Chen K, Jin X, Gonzalez FJ, Liu A. PPARα mediates night neon light-induced weight gain: role of lipid homeostasis. Am J Cancer Res 2020; 10:11497-11506. [PMID: 33052228 PMCID: PMC7545995 DOI: 10.7150/thno.50953] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/21/2020] [Accepted: 08/29/2020] [Indexed: 12/13/2022] Open
Abstract
Rationale: Light pollution leads to high risk of obesity but the underlying mechanism is not known except for the influence of altered circadian rhythm. Peroxisome proliferator-activated receptor α (PPARα) regulates lipid metabolism, but its role in circadian-related obesity is not clear. Methods: Wild-type (WT) and Ppara-null (KO) mice on a high-fat diet (HFD) were treated with neon light at night for 6 weeks. Body weights were recorded and diet consumption measured. The hypothalamus, liver, adipose and serum were collected for mechanism experimentation. Results: WT mice on a HFD and exposed to night neon light gained about 19% body weight more than the WT control mice without light exposure and KO control mice on a HFD and exposed to night neon light. The increase in adipose tissue weight and adipocyte size led to the differences in body weights. Biochemical analysis suggested increased hepatic lipid accumulated and increased transport of lipid from the liver to peripheral tissues in the WT mice that gained weight under neon light exposure. Unlike KO mice, the expression of genes involved in lipid metabolism and the circadian factor circadian locomotor output cycles kaput (CLOCK) in both liver and adipose tissues were elevated in WT mice under neon light exposure. Conclusions: PPARα mediated weight gain of HFD-treated mice exposed to night neon light. More lipids were synthesized in the liver and transported to peripheral tissue leading to adaptive metabolism and lipid deposition in the adipose tissue. These data revealed an important mechanism of obesity induced by artificial light pollution where PPARα was implicated.
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28
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Monfredi O, Lakatta EG. Complexities in cardiovascular rhythmicity: perspectives on circadian normality, ageing and disease. Cardiovasc Res 2020; 115:1576-1595. [PMID: 31150049 DOI: 10.1093/cvr/cvz112] [Citation(s) in RCA: 27] [Impact Index Per Article: 5.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/27/2018] [Revised: 02/06/2019] [Accepted: 05/25/2019] [Indexed: 12/13/2022] Open
Abstract
Biological rhythms exist in organisms at all levels of complexity, in most organs and at myriad time scales. Our own biological rhythms are driven by energy emitted by the sun, interacting via our retinas with brain stem centres, which then send out complex messages designed to synchronize the behaviour of peripheral non-light sensing organs, to ensure optimal physiological responsiveness and performance of the organism based on the time of day. Peripheral organs themselves have autonomous rhythmic behaviours that can act independently from central nervous system control but is entrainable. Dysregulation of biological rhythms either through environment or disease has far-reaching consequences on health that we are only now beginning to appreciate. In this review, we focus on cardiovascular rhythms in health, with ageing and under disease conditions.
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Affiliation(s)
- Oliver Monfredi
- Division of Medicine, Department of Cardiology, The Johns Hopkins Hospital, 1800 Orleans Street, Baltimore, MD, USA.,Laboratory of Cardiovascular Sciences, Intramural Research Program, National Institute on Aging, National Institutes of Health, 251 Bayview Blvd, Baltimore, MD, USA
| | - Edward G Lakatta
- Laboratory of Cardiovascular Sciences, Intramural Research Program, National Institute on Aging, National Institutes of Health, 251 Bayview Blvd, Baltimore, MD, USA
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29
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Ali KM, Abdelgalil AI, Hassan EA, Torad FA. Circadian rhythm of intraocular pressure in clinically normal donkeys (Equus asinus). BIOL RHYTHM RES 2020. [DOI: 10.1080/09291016.2020.1773052] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/24/2022]
Affiliation(s)
- Khaled M. Ali
- Department of Surgery, Anesthesiology and Radiology Faculty of Veterinary Medicine, Cairo University, Cairo, Egypt
| | - Ahmed I. Abdelgalil
- Department of Surgery, Anesthesiology and Radiology Faculty of Veterinary Medicine, Cairo University, Cairo, Egypt
| | - Elham A. Hassan
- Department of Surgery, Anesthesiology and Radiology Faculty of Veterinary Medicine, Cairo University, Cairo, Egypt
| | - Faisal A. Torad
- Department of Surgery, Anesthesiology and Radiology Faculty of Veterinary Medicine, Cairo University, Cairo, Egypt
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30
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Liu WW, Wei SZ, Huang GD, Liu LB, Gu C, Shen Y, Wang XH, Xia ST, Xie AM, Hu LF, Wang F, Liu CF. BMAL1 regulation of microglia-mediated neuroinflammation in MPTP-induced Parkinson's disease mouse model. FASEB J 2020; 34:6570-6581. [PMID: 32246801 DOI: 10.1096/fj.201901565rr] [Citation(s) in RCA: 68] [Impact Index Per Article: 13.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/25/2019] [Revised: 12/21/2019] [Accepted: 03/06/2020] [Indexed: 12/14/2022]
Abstract
Dysfunction of the circadian rhythm is one of most common nonmotor symptoms in Parkinson's disease (PD), but the molecular role of the circadian rhythm in PD is unclear. We here showed that inactivation of brain and muscle ARNT-like 1 (BMAL1) in 1-methyl-4-phenyl-1,2,4,5-tetrahydropyridine (MPTP)-treated mice resulted in obvious motor functional deficit, loss of dopaminergic neurons (DANs) in the substantia nigra pars compacta (SNpc), decrease of dopamine (DA) transmitter, and increased activation of microglia and astrocytes in the striatum. Time on the rotarod or calorie consumption, and food and water intake were reduced in the Bmal1-/- mice after MPTP treatment, suggesting that absence of Bmal1 may exacerbate circadian and PD motor function. We observed a significant reduction of DANs (~35%) in the SNpc, the tyrosine hydroxylase protein level in the striatum (~60%), the DA (~22%), and 3,4-dihydroxyphenylacetic acid content (~29%), respectively, in MPTP-treated Bmal1-/- mice. Loss of Bmal1 aggravated the inflammatory reaction both in vivo and in vitro. These findings suggest that BMAL1 may play an essential role in the survival of DANs and maintain normal function of the DA signaling pathway via regulating microglia-mediated neuroinflammation in the brain.
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Affiliation(s)
- Wen-Wen Liu
- Department of Neurology and Suzhou Clinical Research Center of Neurological Disease, The Second Affiliated Hospital of Soochow University, Suzhou, China
- Jiangsu Key Laboratory of Neuropsychiatric Diseases and Institute of Neuroscience, Soochow University, Suzhou, China
| | - Shi-Zhuang Wei
- Jiangsu Key Laboratory of Neuropsychiatric Diseases and Institute of Neuroscience, Soochow University, Suzhou, China
| | - Guo-Dong Huang
- Department of Neurology, Brigham and Women's Hospital, Harvard Medical School, Boston, USA
| | - Lu-Bing Liu
- Jiangsu Key Laboratory of Neuropsychiatric Diseases and Institute of Neuroscience, Soochow University, Suzhou, China
| | - Chao Gu
- Department of Neurology and Suzhou Clinical Research Center of Neurological Disease, The Second Affiliated Hospital of Soochow University, Suzhou, China
- Jiangsu Key Laboratory of Neuropsychiatric Diseases and Institute of Neuroscience, Soochow University, Suzhou, China
| | - Yun Shen
- Department of Neurology and Suzhou Clinical Research Center of Neurological Disease, The Second Affiliated Hospital of Soochow University, Suzhou, China
| | - Xian-Hui Wang
- Department of Neurology and Suzhou Clinical Research Center of Neurological Disease, The Second Affiliated Hospital of Soochow University, Suzhou, China
- Department of Neurology, Taicang Affiliated Hospital of Soochow University, The First People's Hospital of Taicang, Taicang, China
| | - Shu-Ting Xia
- Jiangsu Key Laboratory of Neuropsychiatric Diseases and Institute of Neuroscience, Soochow University, Suzhou, China
| | - An-Mu Xie
- Department of Neurology, Affiliated Hospital of Qingdao University, Qingdao, China
| | - Li-Fang Hu
- Jiangsu Key Laboratory of Neuropsychiatric Diseases and Institute of Neuroscience, Soochow University, Suzhou, China
| | - Fen Wang
- Jiangsu Key Laboratory of Neuropsychiatric Diseases and Institute of Neuroscience, Soochow University, Suzhou, China
| | - Chun-Feng Liu
- Department of Neurology and Suzhou Clinical Research Center of Neurological Disease, The Second Affiliated Hospital of Soochow University, Suzhou, China
- Jiangsu Key Laboratory of Neuropsychiatric Diseases and Institute of Neuroscience, Soochow University, Suzhou, China
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31
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Rhythm and blues: Influence of CLOCK T3111C on peripheral electrophysiological indicators of negative affective processing. Physiol Behav 2020; 219:112831. [DOI: 10.1016/j.physbeh.2020.112831] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/12/2019] [Revised: 02/03/2020] [Accepted: 02/03/2020] [Indexed: 12/31/2022]
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32
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Knoedler JR, Ávila-Mendoza J, Subramani A, Denver RJ. The Paralogous Krüppel-like Factors 9 and 13 Regulate the Mammalian Cellular Circadian Clock Output Gene Dbp. J Biol Rhythms 2020; 35:257-274. [PMID: 32241200 DOI: 10.1177/0748730420913205] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
An intricate transcription-translation feedback loop (TTFL) governs cellular circadian rhythms in mammals. Here, we report that the zinc finger transcription factor Krüppel-like factor 9 (KLF9) is regulated by this TTFL, it associates in chromatin at the core circadian clock and clock-output genes, and it acts to modulate transcription of the clock-output gene Dbp. Our earlier genome-wide analysis of the mouse hippocampus-derived cell line HT22 showed that KLF9 associates in chromatin with Per1, Per3, Dbp, Tef, Bhlhe40, Bhlhe41, Nr1d1, and Nr1d2. Of the 3514 KLF9 peaks identified in HT22 cells, 1028 contain E-box sequences to which the transcriptional activators CLOCK and BMAL1 may bind, a frequency significantly greater than expected by chance. Klf9 mRNA showed circadian oscillation in synchronized HT22 cells, mouse hippocampus, and liver. At the clock-output gene Dbp, KLF9 exhibited circadian rhythmicity in its association in chromatin in HT22 cells and hippocampus. Forced expression of KLF9 in HT22 cells repressed basal Dbp transcription and strongly inhibited CLOCK+BMAL1-dependent transcriptional activation of a transfected Dbp reporter. Mutational analysis showed that this action of KLF9 depended on 2 intact KLF9-binding motifs within the Dbp locus that are in close proximity to E-boxes. Knockout of Klf9 or the paralogous gene Klf13 using CRISPR/Cas9 genome editing in HT22 cells had no effect on Dbp expression, but combined knockout of both genes strongly impaired circadian Dbp mRNA oscillation. Like KLF9, KLF13 also showed association in chromatin with clock- and clock-output genes, and forced expression of KLF13 inhibited the actions of CLOCK+BMAL1 on Dbp transcription. Our results suggest novel and partly overlapping roles for KLF9 and KLF13 in modulating cellular circadian clock output by a mechanism involving direct interaction with the core TTFL.
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Affiliation(s)
- Joseph R Knoedler
- Neuroscience Graduate Program, The University of Michigan, Ann Arbor, Michigan
| | - José Ávila-Mendoza
- Department of Molecular, Cellular and Developmental Biology, The University of Michigan, Ann Arbor, Michigan
| | - Arasakumar Subramani
- Department of Molecular, Cellular and Developmental Biology, The University of Michigan, Ann Arbor, Michigan
| | - Robert J Denver
- Neuroscience Graduate Program, The University of Michigan, Ann Arbor, Michigan.,Department of Molecular, Cellular and Developmental Biology, The University of Michigan, Ann Arbor, Michigan
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33
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Flôres DEFL, Oda GA. Quantitative Study of Dual Circadian Oscillator Models under Different Skeleton Photoperiods. J Biol Rhythms 2020; 35:302-316. [DOI: 10.1177/0748730420901939] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
The daily proportion of light and dark hours (photoperiod) changes annually and plays an important role in the synchronization of seasonal biological phenomena, such as reproduction, hibernation, and migration. In mammals, the first step of photoperiod transduction occurs in the suprachiasmatic nuclei (SCN), the circadian pacemaker that also coordinates 24-h activity rhythms. Thus, in parallel with its role in annual synchronization, photoperiod variation acutely shapes day/night activity patterns, which vary throughout the year. Systematic studies of this behavioral modulation help understand the mechanisms behind its transduction at the SCN level. To explain how entrainment mechanisms could account for daily activity patterns under different photoperiods, Colin Pittendrigh and Serge Daan proposed a conceptual model in which the pacemaker would be composed of 2 coupled, evening (E) and morning (M), oscillators. Although the E-M model has existed for more than 40 years now, its physiological bases are still not fully resolved, and it has not been tested quantitatively under different photoperiods. To better explore the implications of the E-M model, we performed computer simulations of 2 coupled limit-cycle oscillators. Four model configurations were exposed to systematic variation of skeleton photoperiods, and the resulting daily activity patterns were assessed. The criterion for evaluating different model configurations was the successful reproduction of 2 key behavioral phenomena observed experimentally: activity psi-jumps and photoperiod-induced changes in activity phase duration. We compared configurations with either separate light inputs to E and M or the same light inputs to both oscillators. The former replicated experimental results closely, indicating that the configuration with separate E and M light inputs is the mechanism that best reproduces the effects of different skeleton photoperiods on day/night activity patterns. We hope this model can contribute to the search for E and M and their light input organization in the SCN.
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Affiliation(s)
| | - Gisele A. Oda
- Instituto de Biociências, Universidade de São Paulo, Sao Paulo, Brazil
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34
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The Circadian Clock, the Immune System, and Viral Infections: The Intricate Relationship Between Biological Time and Host-Virus Interaction. Pathogens 2020; 9:pathogens9020083. [PMID: 32012758 PMCID: PMC7168639 DOI: 10.3390/pathogens9020083] [Citation(s) in RCA: 40] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/09/2019] [Revised: 01/22/2020] [Accepted: 01/22/2020] [Indexed: 02/07/2023] Open
Abstract
Living beings spend their lives and carry out their daily activities interacting with environmental situations that present space-time variations and that involve contact with other life forms, which may behave as commensals or as invaders and/or parasites. The characteristics of the environment, as well as the processes that support the maintenance of life and that characterize the execution of activities of daily life generally present periodic variations, which are mostly synchronized with the light–dark cycle determined by Earth’s rotation on its axis. These rhythms with 24-h periodicity, defined as circadian, influence events linked to the interaction between hosts and hosted microorganisms and can dramatically determine the outcome of this interplay. As for the various pathological conditions resulting from host–microorganism interactions, a particularly interesting scenario concerns infections by viruses. When a viral agent enters the body, it alters the biological processes of the infected cells in order to favour its replication and to spread to various tissues. Though our knowledge concerning the mutual influence between the biological clock and viruses is still limited, recent studies start to unravel interesting aspects of the clock–virus molecular interplay. Three different aspects of this interplay are addressed in this mini-review and include the circadian regulation of both innate and adaptive immune systems, the impact of the biological clock on viral infection itself, and finally the putative perturbations that the virus may confer to the clock leading to its deregulation.
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35
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Camello-Almaraz C, Martin-Cano FE, Santos FJ, Espin MT, Antonio Madrid J, Pozo MJ, Camello PJ. Age-Induced Differential Changes in the Central and Colonic Human Circadian Oscillators. Int J Mol Sci 2020; 21:ijms21020674. [PMID: 31968581 PMCID: PMC7013976 DOI: 10.3390/ijms21020674] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/08/2019] [Revised: 01/10/2020] [Accepted: 01/16/2020] [Indexed: 12/31/2022] Open
Abstract
Aging modifies not only multiple cellular and homeostatic systems, but also biological rhythms. The circadian system is driven by a central hypothalamic oscillator which entrains peripheral oscillators, in both cases underlain by circadian genes. Our aim was to characterize the effect of aging in the circadian expression of clock genes in the human colon. Ambulatory recordings of the circadian rhythms of skin wrist temperature, motor activity and the integrated variable TAP (temperature, activity and position) were dampened by aging, especially beyond 74 years of age. On the contrary, quantitative analysis of genes expression in the muscle layer of colonic explants during 24 h revealed that the circadian expression of Bmal1, Per1 and Clock genes, was larger beyond that age. In vitro experiments showed that aging induced a parallel increase in the myogenic contractility of the circular colonic muscle. This effect was not accompanied by enhancement of Ca2+ signals. In conclusion, we describe here for the first time the presence of a molecular oscillator in the human colon. Aging has a differential effect on the systemic circadian rhythms, that are impaired by aging, and the colonic oscillator, that is strengthened in parallel with the myogenic contractility.
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Affiliation(s)
- Cristina Camello-Almaraz
- Department of Physiology, Institute of Molecular Pathology Biomarkers, University of Extremadura, Campus Universitario, 10003 Cáceres, Spain; (C.C.-A.); (F.E.M.-C.); (M.J.P.)
| | - Francisco E. Martin-Cano
- Department of Physiology, Institute of Molecular Pathology Biomarkers, University of Extremadura, Campus Universitario, 10003 Cáceres, Spain; (C.C.-A.); (F.E.M.-C.); (M.J.P.)
| | - Francisco J. Santos
- Surgery Department, University Hospital, Servicio Extremeño de Salud, Avda Universidad, 10004 Cáceres, Spain;
| | - Mª Teresa Espin
- Faculty of Medicine, Infanta Cristina University Hospital, Servicio Extremeño de Salud, Avda Elbas, 06080 Badajoz, Spain;
| | - Juan Antonio Madrid
- Chronobiology Lab, Department of Physiology, College of Biology, University of Murcia, Mare Nostrum Campus, IMIB-Arrixaca, 30100 Murcia, Spain;
| | - Maria J. Pozo
- Department of Physiology, Institute of Molecular Pathology Biomarkers, University of Extremadura, Campus Universitario, 10003 Cáceres, Spain; (C.C.-A.); (F.E.M.-C.); (M.J.P.)
| | - Pedro J. Camello
- Department of Physiology, Institute of Molecular Pathology Biomarkers, University of Extremadura, Campus Universitario, 10003 Cáceres, Spain; (C.C.-A.); (F.E.M.-C.); (M.J.P.)
- Correspondence:
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36
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Carvalho FG, Cunha AMD, Tonon AC, Pereira FDS, Matte U, Callegari-Jacques SM, Hidalgo MP. Poor sleep quality associates with self-reported psychiatric and cardiometabolic symptoms independently of sleep timing patterns in a large sample of rural and urban workers. J Sleep Res 2020; 29:e12969. [PMID: 31909859 DOI: 10.1111/jsr.12969] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/10/2019] [Revised: 11/08/2019] [Accepted: 11/23/2019] [Indexed: 12/19/2022]
Abstract
Poor sleep associates with mental and cardiometabolic pathological outcomes. The participation of sleep timing features in the pathways by which this relationship occurs is not clear. This study aims to evaluate the interrelationship between sleep quality and self-reported psychiatric/cardiometabolic symptoms, considering mediation and moderation effects of sleep timing patterns, and urban versus rural work environment, respectively; and to verify the association between sleep quality and polymorphisms of AANAT, RORA and TIMELESS genes. An epidemiological survey was performed in a rural area in southern Brazil. Eight-hundred and twenty-nine subjects were evaluated for sleep quality using the Pittsburgh Sleep Quality Index, and sleep timing patterns using the Munich Chronotype Questionnaire. Work characteristics and psychiatric/cardiometabolic symptoms were assessed using a structured self-report questionnaire. Three polymorphisms of AANAT, RORA and TIMELESS (rs3760138, rs782931 and rs774045, respectively) were genotyped in blood samples. We found statistically significant associations of poor sleep quality with self-reported psychiatric symptoms (B = 0.382; 95% CI 0.289-0.476; adjusted p-value <.001), and with self-reported cardiometabolic symptoms (B = 0.079; 95% CI 0.013-0.151; adjusted p-value = .048). The genetic analysis showed that RORA GA/AA genotype was associated to poor sleep quality (B = 0.146, 95% CI 0.054-0.239; adjusted p-value = .004). No moderated mediation effects were observed in the conditional analysis. TIMELESS polymorphism was not included in the analysis due to the low frequency of risk genotypes. These results yield new insights regarding the interrelationship between sleep characteristics and psychiatric/cardiometabolic self-reported symptoms, taking into account genes related to the biological clocks and melatonin pathways.
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Affiliation(s)
- Felipe Gutiérrez Carvalho
- Laboratório de Cronobiologia e Sono, Hospital de Clínicas de Porto Alegre (HCPA)/Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, Brazil.,Graduate Program in Psychiatry and Behavioral Sciences, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, Brazil
| | - Ana Maria Delgado Cunha
- Laboratório de Cronobiologia e Sono, Hospital de Clínicas de Porto Alegre (HCPA)/Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, Brazil
| | - André Comiran Tonon
- Laboratório de Cronobiologia e Sono, Hospital de Clínicas de Porto Alegre (HCPA)/Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, Brazil.,Graduate Program in Psychiatry and Behavioral Sciences, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, Brazil
| | - Fernanda Dos Santos Pereira
- Centro de Pesquisa Experimental, Unidade de Análises Moleculares e de Proteínas (UAMP), Hospital de Clínicas de Porto Alegre (HCPA), Porto Alegre, Brazil
| | - Ursula Matte
- Gene Therapy Center, Experimental Research Center, Hospital de Clínicas de Porto Alegre (HCPA), Porto Alegre, Brazil
| | - Sidia Maria Callegari-Jacques
- Departamento de Estatística, Instituto de Matemática e Estatística, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, Brazil
| | - Maria Paz Hidalgo
- Laboratório de Cronobiologia e Sono, Hospital de Clínicas de Porto Alegre (HCPA)/Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, Brazil.,Graduate Program in Psychiatry and Behavioral Sciences, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, Brazil
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Bates K, Herzog ED. Maternal-Fetal Circadian Communication During Pregnancy. Front Endocrinol (Lausanne) 2020; 11:198. [PMID: 32351448 PMCID: PMC7174624 DOI: 10.3389/fendo.2020.00198] [Citation(s) in RCA: 47] [Impact Index Per Article: 9.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/11/2019] [Accepted: 03/19/2020] [Indexed: 12/21/2022] Open
Abstract
This article reviews evidence for maternal-fetal communication about the time of day. We explore the hypothesis that key maternal hormones synchronize daily rhythms in the fetus to regulate gestation duration. These findings may help to predict and prevent preterm birth.
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Yang T, Yuan P, Yang Y, Liang N, Wang Q, Li J, Lu R, Zhang H, Mu J, Yan Z, Chang H. NPAS2 Contributes to Liver Fibrosis by Direct Transcriptional Activation of Hes1 in Hepatic Stellate Cells. MOLECULAR THERAPY. NUCLEIC ACIDS 2019; 18:1009-1022. [PMID: 31778954 PMCID: PMC6889679 DOI: 10.1016/j.omtn.2019.10.025] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 09/20/2019] [Accepted: 10/23/2019] [Indexed: 12/29/2022]
Abstract
Recently, emerging evidence shows that dysregulation of circadian genes is closely associated with liver fibrosis. However, how dysregulation of circadian genes promotes liver fibrosis is unknown. In this study, we show that neuronal PAS domain protein 2 (NPAS2), one of the core circadian molecules that has been shown to promote hepatocarcinoma cell proliferation, significantly contributed to liver fibrogenesis. NPAS2 is upregulated in hepatic stellate cells (HSCs) after fibrogenic injury, which subsequently contributes to the activation of HSCs. Mechanistically, NPAS2 plays a profibrotic role via direct transcriptional activation of hairy and enhancer of split 1 (Hes1), a critical transcriptor of Notch signaling for the fibrogenesis process, in HSCs. Our findings demonstrate that NPAS2 plays a critical role in liver fibrosis through direct transcriptional activation of Hes1, indicating that NPAS2 may serve as an important therapeutic target to reverse the progression of liver fibrosis.
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Affiliation(s)
- Tao Yang
- Department of Pain Treatment, Tangdu Hospital, The Fourth Military Medical University, Xi'an, Shaanxi 710038, China
| | - Peng Yuan
- State Key Laboratory of Cancer Biology and Experimental Teaching Center of Basic Medicine, The Fourth Military Medical University, Xi'an, Shaanxi 710032, China
| | - Yi Yang
- Department of Pain Treatment, Tangdu Hospital, The Fourth Military Medical University, Xi'an, Shaanxi 710038, China
| | - Ning Liang
- Department of General Surgery, The 75th Group Army Hospital, Dali, Yunnan 671000, China
| | - Qian Wang
- Department of General Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, China
| | - Jing Li
- College and Hospital of Stomatology, Xi'an Jiaotong University, Xi'an, Shaanxi 710004, China
| | - Rui Lu
- Department of Pain Treatment, Tangdu Hospital, The Fourth Military Medical University, Xi'an, Shaanxi 710038, China
| | - Hongxin Zhang
- Department of Pain Treatment, Tangdu Hospital, The Fourth Military Medical University, Xi'an, Shaanxi 710038, China
| | - Jiao Mu
- Department of Hematology, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China; Department of Hematology, Xi'an Central Hospital, Xi'an, Shaanxi 710003, China.
| | - Zhaoyong Yan
- Department of Pain Treatment, Tangdu Hospital, The Fourth Military Medical University, Xi'an, Shaanxi 710038, China.
| | - Hulin Chang
- Department of Hepatobiliary Surgery, Shaanxi Provincial People's Hospital, Xi'an 710068, China.
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Dardente H, Lomet D, Chesneau D, Pellicer-Rubio MT, Hazlerigg D. Discontinuity in the molecular neuroendocrine response to increasing daylengths in Ile-de-France ewes: Is transient Dio2 induction a key feature of circannual timing? J Neuroendocrinol 2019; 31:e12775. [PMID: 31340078 DOI: 10.1111/jne.12775] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/22/2019] [Revised: 07/15/2019] [Accepted: 07/17/2019] [Indexed: 12/21/2022]
Abstract
In mammals, melatonin is responsible for the synchronisation of seasonal cycles to the solar year. Melatonin is secreted by the pineal gland with a profile reflecting the duration of the night and acts via the pituitary pars tuberalis (PT), which in turn modulates hypothalamic thyroid hormone status via seasonal changes in the production of locally-acting thyrotrophin. Recently, we demonstrated that, in the Soay sheep, photoperiodic induction of Tshb expression and consequent downstream hypothalamic changes occur over a narrow range of photoperiods between 12 and 14 hours in duration. In the present study, we aimed to extend our molecular characterisation of this pathway, based on transcriptomic analysis of photoperiodic changes in the pituitary and hypothalamus of ovariectomised, oestradiol-implanted Ile-de-France ewes. We demonstrate that photoperiodic treatments applied before the winter solstice elicit two distinctive modes of accelerated reproductive switch off compared to ewes held on a simulated natural photoperiod, with shut-down occurring markedly faster on photoperiods of 13 hours or more than on photoperiods of 12 hours and less. This pattern of response was reflected in gene expression profiles of photoperiodically sensitive markers, both in the PT (Tshb, Fam150b, Vmo1, Ezh2 and Suv39H2) and in tanycytes (Tmem252 and Dct). Unexpectedly, the expression of Dio2 in tanycytes did not show any noticeable increase in expression with lengthening photoperiods. Finally, the expression of Kiss1, the key activator of gonadotrophin-releasing hormone release, was proportionately decreased by lengthening photoperiods, in a pattern that correlated strongly with gonadotrophin suppression. These data show that stepwise increases in photoperiod lead to graded molecular responses at the level of the PT, a progressive suppression of Kiss1 in the hypothalamic arcuate nucleus and luteinising hormone/follicle-stimulating hormone release by the pituitary, despite apparently unchanged Dio2 expression in tanycytes. We hypothesise that this apparent discontinuity in the seasonal neuroendocrine response illustrates the transient nature of the thyroid hormone-mediated response to long days in the control of circannual timing.
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Affiliation(s)
- Hugues Dardente
- PRC, INRA, CNRS, IFCE, Université de Tours, Nouzilly, France
| | - Didier Lomet
- PRC, INRA, CNRS, IFCE, Université de Tours, Nouzilly, France
| | - Didier Chesneau
- PRC, INRA, CNRS, IFCE, Université de Tours, Nouzilly, France
| | | | - David Hazlerigg
- Department of Arctic and Marine Biology, University of Tromsø, Tromsø, Norway
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Nitta Y, Matsui S, Kato Y, Kaga Y, Sugimoto K, Sugie A. Analysing the evolutional and functional differentiation of four types of Daphnia magna cryptochrome in Drosophila circadian clock. Sci Rep 2019; 9:8857. [PMID: 31222139 PMCID: PMC6586792 DOI: 10.1038/s41598-019-45410-w] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/11/2018] [Accepted: 06/06/2019] [Indexed: 12/02/2022] Open
Abstract
Cryptochrome (CRY) plays an important role in the input of circadian clocks in various species, but gene copies in each species are evolutionarily divergent. Type I CRYs function as a photoreceptor molecule in the central clock, whereas type II CRYs directly regulate the transcriptional activity of clock proteins. Functions of other types of animal CRYs in the molecular clock remain unknown. The water flea Daphnia magna contains four Cry genes. However, it is still difficult to analyse these four genes. In this study, we took advantage of powerful genetic resources available from Drosophila to investigate evolutionary and functional differentiation of CRY proteins between the two species. We report differences in subcellular localisation of each D. magna CRY protein when expressed in the Drosophila clock neuron. Circadian rhythm behavioural experiments revealed that D. magna CRYs are not functionally conserved in the Drosophila molecular clock. These findings provide a new perspective on the evolutionary conservation of CRY, as functions of the four D. magna CRY proteins have diverse subcellular localisation levels. Furthermore, molecular clocks of D. magna have been evolutionarily differentiated from those of Drosophila. This study highlights the extensive functional diversity existing among species in their complement of Cry genes.
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Affiliation(s)
- Yohei Nitta
- Center for Transdisciplinary Research, Niigata University, Niigata, Japan
- Brain Research Institute, Niigata University, Niigata, Japan
| | - Sayaka Matsui
- Department of Cell Science, Faculty of Graduate School of Science and Technology, Niigata University, Niigata, Japan
| | - Yukine Kato
- Department of Cell Science, Faculty of Graduate School of Science and Technology, Niigata University, Niigata, Japan
| | - Yosuke Kaga
- School of Medicine, Niigata University, Niigata, Japan
| | - Kenkichi Sugimoto
- Department of Cell Science, Faculty of Graduate School of Science and Technology, Niigata University, Niigata, Japan.
| | - Atsushi Sugie
- Center for Transdisciplinary Research, Niigata University, Niigata, Japan.
- Brain Research Institute, Niigata University, Niigata, Japan.
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Melia T, Waxman DJ. Sex-Biased lncRNAs Inversely Correlate With Sex-Opposite Gene Coexpression Networks in Diversity Outbred Mouse Liver. Endocrinology 2019; 160:989-1007. [PMID: 30840070 PMCID: PMC6449536 DOI: 10.1210/en.2018-00949] [Citation(s) in RCA: 21] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/07/2018] [Accepted: 02/27/2019] [Indexed: 01/05/2023]
Abstract
Sex differences in liver gene expression are determined by pituitary growth hormone secretion patterns, which regulate sex-dependent liver transcription factors and establish sex-specific chromatin states. Hypophysectomy (hypox) identifies two major classes of liver sex-biased genes, defined by their sex-dependent positive or negative responses to pituitary hormone ablation. However, the mechanisms that underlie each hypox-response class are unknown. We sought to discover candidate, regulatory, long noncoding RNAs (lncRNAs) controlling responsiveness to hypox. We characterized gene structures and expression patterns for 15,558 mouse liver-expressed lncRNAs, including many sex-specific lncRNAs regulated during postnatal development or subject to circadian regulation. Using the high natural allelic variance of Diversity Outbred (DO) mice, we discovered tightly coexpressed clusters of sex-specific protein-coding genes (gene modules) in male and female DO liver. Remarkably, many gene modules were strongly enriched for sex-specific genes within a single hypox-response class, indicating that the genetic heterogeneity of DO mice encompasses responsiveness to hypox. Moreover, several distant gene modules were enriched for gene subsets of the same hypox-response class, highlighting the complex regulation of hypox-responsiveness. Finally, we identified eight sex-specific lncRNAs with strong negative regulatory potential, as indicated by their strong negative correlation of expression across DO mouse livers with that of protein-coding gene modules enriched for genes of the opposite sex bias and inverse hypox-response class. These findings reveal an important role for genetic factors in regulating responsiveness to hypox, and present testable hypotheses for the roles of sex-biased liver lncRNAs in controlling the sex-bias of liver gene expression.
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Affiliation(s)
- Tisha Melia
- Department of Biology and Bioinformatics Program, Boston University, Boston, Massachusetts
| | - David J Waxman
- Department of Biology and Bioinformatics Program, Boston University, Boston, Massachusetts
- Correspondence: David J. Waxman, PhD, Department of Biology, Boston University, 5 Cummington Mall, Boston, Massachusetts 02215. E-mail:
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Bargi-Souza P, Peliciari-Garcia RA, Nunes MT. Disruption of the Pituitary Circadian Clock Induced by Hypothyroidism and Hyperthyroidism: Consequences on Daily Pituitary Hormone Expression Profiles. Thyroid 2019; 29:502-512. [PMID: 30747053 DOI: 10.1089/thy.2018.0578] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
BACKGROUND The secretion of pituitary hormones oscillates throughout the 24-hour period, indicating that circadian clock-mediated mechanisms regulate this process in the gland. Additionally, pituitary hormone synthesis has been shown to be altered in hypo- and hyperthyroidism. Although thyroid hormones can modulate the other peripheral clocks, the interaction between thyroid hormone levels and circadian clock gene expression in the anterior pituitary has yet to be elucidated. METHODS Male Wistar rats were divided into three groups: control, hypothyroid, and hyperthyroid. Following the experimental procedures, animals were euthanized every three hours over the course of a 24-hour period. The anterior pituitary glands were excised and processed for mRNA expression analysis by quantitative reverse transcriptase polymerase chain reaction. One- and two-way analysis of variance as well as cosinor analysis were used to evaluate the time-of-day-dependent differential expression for each gene in each experimental group and their interactions. RESULTS Hyperthyroidism increased the mRNA expression of core clock genes and thyrotrophic embryonic factor (Tef), as well as the mesor and amplitude of brain and muscle Arnt-like protein-1 (Bmal1) and the mesor of nuclear receptor subfamily 1 (Nr1d1) group D member 1, when compared to euthyroid animals. Hypothyroidism disrupted the circadian expression pattern of Bmal1 and period circadian regulator 2 (Per2) and decreased the mesor of Nr1d1 and Tef. Furthermore, it was observed that the pituitary content of Dio2 mRNA was unaltered in hyperthyroidism but substantially elevated in hypothyroidism during the light phase. The upregulated expression was associated with an increased mesor and amplitude, along with an advanced acrophase. The gene expression of all the pituitary hormones was found to be altered in hypo- and hyperthyroidism. Moreover, prolactin (Prl) and luteinizing hormone beta subunit (Lhb) displayed circadian expression patterns in the control group, which were disrupted in both the hypo- and hyperthyroid states. CONCLUSION Taken together, the data demonstrate that hypo- and hyperthyroidism alter circadian clock gene expression in the anterior pituitary. This suggests that triiodothyronine plays an important role in the regulation of pituitary gland homeostasis, which could ultimately influence the rhythmic synthesis and/or secretion of all the anterior pituitary hormones.
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Affiliation(s)
- Paula Bargi-Souza
- 1 Department of Physiology and Biophysics, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil
| | - Rodrigo A Peliciari-Garcia
- 2 Morphophysiology and Pathology Sector, Department of Biological Sciences, Federal University of São Paulo, Diadema, Brazil
| | - Maria Tereza Nunes
- 1 Department of Physiology and Biophysics, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil
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Ashraf H, Ahmad J, Hassan A, Ali A. Computational modeling and analysis of the impacts of sleep deprivation on glucose stimulated insulin secretion. Biosystems 2019; 179:1-14. [PMID: 30790613 DOI: 10.1016/j.biosystems.2019.02.005] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/26/2018] [Revised: 01/02/2019] [Accepted: 02/13/2019] [Indexed: 01/12/2023]
Abstract
Circadian clock is an exquisite internal biological clock functioning in all living organisms. Lifestyle changes such as shift work or frequent travelling might result in malfunctioning of the central and consequently the peripheral clocks leading to different metabolic disorders. Disruptions in β cell clock have been found to be a potential reason behind β cell failure that makes a person prone towards developing type 2 diabetes (T2DM). In this study, a Petri net model for β cell circadian clock has been developed, followed by analysis of the negative impacts of sleep deprivation conditions on the process of glucose stimulated insulin secretion (GSIS) through misalignment of circadian clock. The analysis of structural properties of the Petri net model reveals robustness of the circadian system. The simulation results predict that sleep loss negatively affects the expression of circadian genes which eventually leads to impaired GSIS and β cell failure. These results suggest that sleep/wake cycle is a vital contributor for the entrainment of the circadian clock and normal functioning of β cell.
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Affiliation(s)
- Hufsah Ashraf
- Research Center for Modeling and Simulation (RCMS), National University of Sciences and Technology (NUST), Islamabad, Pakistan
| | - Jamil Ahmad
- Research Center for Modeling and Simulation (RCMS), National University of Sciences and Technology (NUST), Islamabad, Pakistan; Department of Computer Science and Information Technology, University of Malakand, Chakdara, Pakistan.
| | - Azka Hassan
- Research Center for Modeling and Simulation (RCMS), National University of Sciences and Technology (NUST), Islamabad, Pakistan
| | - Amjad Ali
- Atta-Ur-Rahman School of Applied Biosciences, National University of Sciences and Technology (NUST), Islamabad, Pakistan
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Fang H, Tu S, Sheng J, Shao A. Depression in sleep disturbance: A review on a bidirectional relationship, mechanisms and treatment. J Cell Mol Med 2019; 23:2324-2332. [PMID: 30734486 PMCID: PMC6433686 DOI: 10.1111/jcmm.14170] [Citation(s) in RCA: 613] [Impact Index Per Article: 102.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/15/2018] [Revised: 11/28/2018] [Accepted: 12/29/2018] [Indexed: 02/06/2023] Open
Abstract
Sleep disturbance is the most prominent symptom in depressive patients and was formerly regarded as a main secondary manifestation of depression. However, many longitudinal studies have identified insomnia as an independent risk factor for the development of emerging or recurrent depression among young, middle‐aged and older adults. This bidirectional association between sleep disturbance and depression has created a new perspective that sleep problems are no longer an epiphenomenon of depression but a predictive prodromal symptom. In this review, we highlight the treatment of sleep disturbance before, during and after depression, which probably plays an important role in improving outcomes and preventing the recurrence of depression. In clinical practice, pharmacological therapies, including hypnotics and antidepressants, and non‐pharmacological therapies are typically applied. A better understanding of the pathophysiological mechanisms between sleep disturbance and depression can help psychiatrists better manage this comorbidity.
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Affiliation(s)
- Hong Fang
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou City, Zhejiang Province, China
| | - Sheng Tu
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou City, Zhejiang Province, China
| | - Jifang Sheng
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou City, Zhejiang Province, China
| | - Anwen Shao
- Department of Neurosurgery, Second Affiliated Hospital School of Medicine, Zhejiang University, Hangzhou City, Zhejiang Province, China
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Abstract
The hypothalamus is the brain region responsible for the maintenance of energetic homeostasis. The regulation of this process arises from the ability of the hypothalamus to orchestrate complex physiological responses such as food intake and energy expenditure, circadian rhythm, stress response, and fertility. Metabolic alterations such as obesity can compromise these hypothalamic regulatory functions. Alterations in circadian rhythm, stress response, and fertility further contribute to aggravate the metabolic dysfunction of obesity and contribute to the development of chronic disorders such as depression and infertility.At cellular level, obesity caused by overnutrition can damage the hypothalamus promoting inflammation and impairing hypothalamic neurogenesis. Furthermore, hypothalamic neurons suffer apoptosis and impairment in synaptic plasticity that can compromise the proper functioning of the hypothalamus. Several factors contribute to these phenomena such as ER stress, oxidative stress, and impairments in autophagy. All these observations occur at the same time and it is still difficult to discern whether inflammatory processes are the main drivers of these cellular dysfunctions or if the hypothalamic hormone resistance (insulin, leptin, and ghrelin) can be pinpointed as the source of several of these events.Understanding the mechanisms that underlie the pathophysiology of obesity in the hypothalamus is crucial for the development of strategies that can prevent or attenuate the deleterious effects of obesity.
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Insights into the Role of Circadian Rhythms in Bone Metabolism: A Promising Intervention Target? BIOMED RESEARCH INTERNATIONAL 2018; 2018:9156478. [PMID: 30363685 PMCID: PMC6180976 DOI: 10.1155/2018/9156478] [Citation(s) in RCA: 39] [Impact Index Per Article: 5.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 06/28/2018] [Accepted: 09/09/2018] [Indexed: 11/18/2022]
Abstract
Numerous physiological processes of mammals, including bone metabolism, are regulated by the circadian clock system, which consists of a central regulator, the suprachiasmatic nucleus (SCN), and the peripheral oscillators of the BMAL1/CLOCK-PERs/CRYs system. Various bone turnover markers and bone metabolism-regulating hormones such as melatonin and parathyroid hormone (PTH) display diurnal rhythmicity. According to previous research, disruption of the circadian clock due to shift work, sleep restriction, or clock gene knockout is associated with osteoporosis or other abnormal bone metabolism, showing the importance of the circadian clock system for maintaining homeostasis of bone metabolism. Moreover, common causes of osteoporosis, including postmenopausal status and aging, are associated with changes in the circadian clock. In our previous research, we found that agonism of the circadian regulators REV-ERBs inhibits osteoclast differentiation and ameliorates ovariectomy-induced bone loss in mice, suggesting that clock genes may be promising intervention targets for abnormal bone metabolism. Moreover, osteoporosis interventions at different time points can provide varying degrees of bone protection, showing the importance of accounting for circadian rhythms for optimal curative effects in clinical treatment of osteoporosis. In this review, we summarize current knowledge about circadian rhythms and bone metabolism.
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Onaolapo AY, Onaolapo OJ. Circadian dysrhythmia-linked diabetes mellitus: Examining melatonin’s roles in prophylaxis and management. World J Diabetes 2018; 9:99-114. [PMID: 30079146 PMCID: PMC6068738 DOI: 10.4239/wjd.v9.i7.99] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/15/2018] [Revised: 06/01/2018] [Accepted: 06/08/2018] [Indexed: 02/05/2023] Open
Abstract
Diabetes mellitus is a chronic, life-threatening metabolic disorder that occurs worldwide. Despite an increase in the knowledge of the risk factors that are associated with diabetes mellitus, its worldwide prevalence has continued to rise; thus, necessitating more research into its aetiology. Recent researches are beginning to link a dysregulation of the circadian rhythm to impairment of intermediary metabolism; with evidences that circadian rhythm dysfunction might play an important role in the aetiology, course or prognosis of some cases of diabetes mellitus. These evidences thereby suggest possible relationships between the circadian rhythm regulator melatonin, and diabetes mellitus. In this review, we discuss the roles of the circadian rhythm in the regulation of the metabolism of carbohydrates and other macronutrients; with emphasis on the importance of melatonin and the impacts of its deficiency on carbohydrate homeostasis. Also, the possibility of using melatonin and its analogs for the “prophylaxis” or management of diabetes mellitus is also considered.
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Affiliation(s)
- Adejoke Y Onaolapo
- Behavioural Neuroscience/Neurobiology Unit, Department of Anatomy, Ladoke Akintola University of Technology, Ogbomosho 210211, Oyo State, Nigeria
| | - Olakunle J Onaolapo
- Behavioural Neuroscience/Neuropharmacology Unit, Department of Pharmacology, Ladoke Akintola University of Technology, Osogbo 230263, Osun State, Nigeria
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Cingi C, Emre IE, Muluk NB. Jetlag related sleep problems and their management: A review. Travel Med Infect Dis 2018; 24:59-64. [PMID: 29787851 DOI: 10.1016/j.tmaid.2018.05.008] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/01/2018] [Revised: 05/14/2018] [Accepted: 05/18/2018] [Indexed: 01/13/2023]
Abstract
OBJECTIVES We reviewed Jetlag, particularly in view of its effects on sleep and how it can be managed. METHODS The Proquest Central database of Kırıkkale University, PubMed and Google scholar were used while searching for the following key words: "Jetlag", "symptoms", "sleep", "melatonin" and "treatment". RESULTS Flight dysrhythmia, otherwise known as jetlag, is caused by flying globally over various time zones. Most passengers who fly over six or more different time zones generally require 4-6 days after travelling to resume their usual sleep patterns and to feel less lethargic during the day. Signs of jet lag can vary between debilitated awareness, insomnia, feeling tired during the day and frequent waking during the night. During the night our pineal glands excrete a hormone called melatonin; dim lights cause the continuation of excretion of these hormones whereas any exposure to bright lights stems the flow of release. Common precautionary measures are specific diets, bright lights and melatonin agonists (Ramelteon, Agomelatine). CONCLUSION Sleep issues derived from jetlag were found to be most common in passengers who flew through various time belts. Melatonin assumes a critical part in adjusting the body's circadian rhythms and has been utilized restoratively to re-establish irritated circadian rhythms.
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Affiliation(s)
- Cemal Cingi
- Eskisehir Osmangazi University, Faculty of Medicine, Department of Otorhinolaryngology, Eskisehir, Turkey.
| | - Ismet Emrah Emre
- Acıbadem University, Faculty of Medicine, Department of Otorhinolaryngology, Istanbul, Turkey.
| | - Nuray Bayar Muluk
- Kirikkale University, Faculty of Medicine, Department of Otorhinolaryngology, Kirikkale, Turkey.
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Zhu Z, Xu L, Cai T, Yuan G, Sun N, Lu C, Qian R. Clock represses preadipocytes adipogenesis via GILZ. J Cell Physiol 2018; 233:6028-6040. [PMID: 29278648 DOI: 10.1002/jcp.26420] [Citation(s) in RCA: 30] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/27/2017] [Accepted: 12/20/2017] [Indexed: 02/06/2023]
Abstract
Adiposity is a worldwide health threat that needs to be prevented. Circadian gene Clock (circadian locomotor output cycles kaput) is closely correlated to adiposity; for example, weight gain, adipocytes size expansion, and serum lipid level rise in ClockΔ19 mice compared to C57BL/6J mice. However, the precise role of Clock during adipogenic differentiation is unknown. Herein, the circadian gene Clock is shown to regulate adipogenesis mediated by GILZ. Clock-mediated attenuation and upregulation influenced lipid synthesis and affected the levels of adipogenic transcriptional factors, C/EBP-β, C/EBP-α, PPAR-γ, and FABP4, both in vivo and in vitro (primary adipose-derived stromal cells and 3T3-L1 cells). Chromatin immunoprecipitation (ChIP) assay, reporter gene assay, and serum shock assay found that Clock transcriptionally regulated the glucocorticoid-induced leucine zipper (GILZ). Furthermore, GILZ attenuation could relieve the inhibitory effect of Clock on lipid synthesis and GILZ overexpression also reduced the promotion role of Clock attenuation in adipogenesis suggesting that Clock inhibits adipogenic differentiation of preadipocytes via GILZ. The current results demonstrate how circadian genes are likely to regulate adiposity, affecting the adipogenic differentiation process, as well as, increasing the fat cells number. Therefore, this study may provide novel insights into the underlying mechanism explaining the correlation between Clock mutation and adiposity.
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Affiliation(s)
- Zhu Zhu
- Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Fudan University, Shanghai, China.,Department of BioBank, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China
| | - Lirong Xu
- Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Fudan University, Shanghai, China
| | - Tingting Cai
- Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Fudan University, Shanghai, China
| | - Gongsheng Yuan
- Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Fudan University, Shanghai, China
| | - Ning Sun
- Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Fudan University, Shanghai, China.,Research Center on Aging and Medicine, Fudan University, Shanghai, China
| | - Chao Lu
- Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Fudan University, Shanghai, China.,Research Center on Aging and Medicine, Fudan University, Shanghai, China
| | - Ruizhe Qian
- Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Fudan University, Shanghai, China.,Research Center on Aging and Medicine, Fudan University, Shanghai, China
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Jacobsen JHW, Buisman-Pijlman FTA, Mustafa S, Rice KC, Hutchinson MR. The efficacy of (+)-Naltrexone on alcohol preference and seeking behaviour is dependent on light-cycle. Brain Behav Immun 2018; 67:181-193. [PMID: 28864261 PMCID: PMC7387101 DOI: 10.1016/j.bbi.2017.08.021] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/22/2017] [Revised: 08/18/2017] [Accepted: 08/28/2017] [Indexed: 02/06/2023] Open
Abstract
Circadian rhythm affects drug-induced reward behaviour and the innate immune system. Peaks in reward-associated behaviour and immune responses typically occur during the active (dark) phase of rodents. While the role of the immune system, specifically, Toll-like receptor 4 (TLR4, an innate immune receptor) in drug-induced reward is becoming increasingly appreciated, it is unclear whether its effects vary according to light-cycle. Therefore, the aim of this study was to characterise the effects of the phase of the light-cycle and the state of the innate immune system on alcohol reward behaviour and subsequently determine whether the efficacy of targeting the immune component of drug reward depends upon the light-cycle. This study demonstrates that mice exhibit greater alcohol-induced conditioned place preference and alcohol two-bottle choice preference during the dark cycle. This effect overlapped with elevations in reward-, thirst- and immune-related genes. Administration of (+)-Naltrexone, a TLR4 antagonist, reduced immune-related gene mRNA expression and alcohol preference with its effects most pronounced during the dark cycle. However, (+)-Naltrexone, like other TLR4 antagonists exhibited off-target side effects, with a significant reduction in overall saccharin intake - an effect likely attributable to a reduction in tyrosine hydroxylase (Th) mRNA expression levels. Collectively, the study highlights a link between a time-of-day dependent influence of TLR4 on natural and alcohol reward-like behaviour in mice.
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Affiliation(s)
- Jonathan Henry W Jacobsen
- Discipline of Pharmacology, Adelaide Medical School, University of Adelaide, South Australia, Australia
| | - Femke T A Buisman-Pijlman
- Discipline of Pharmacology, Adelaide Medical School, University of Adelaide, South Australia, Australia
| | - Sanam Mustafa
- Discipline of Physiology, Adelaide Medical School, University of Adelaide, South Australia, Australia; ARC Centre of Excellence for Nanoscale Biophotonics, University of Adelaide, South Australia, Australia
| | - Kenner C Rice
- Drug Design and Synthesis Section, NIDA, Rockville, MD, USA
| | - Mark R Hutchinson
- Discipline of Physiology, Adelaide Medical School, University of Adelaide, South Australia, Australia; ARC Centre of Excellence for Nanoscale Biophotonics, University of Adelaide, South Australia, Australia.
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