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昼夜节律对大脑多巴胺回路的影响:生物钟基因表达的纹状体节律调节及其对精神病理学和疾病的影响。

Circadian influences on dopamine circuits of the brain: regulation of striatal rhythms of clock gene expression and implications for psychopathology and disease.

作者信息

Verwey Michael, Dhir Sabine, Amir Shimon

机构信息

Center for Studies in Behavioural Neurobiology, FRQS Groupe de Recherche en Neurobiologie Comportementale, Concorida University, Montreal, Quebec, Canada.

McGill University, Montreal, Quebec, Canada.

出版信息

F1000Res. 2016 Aug 24;5. doi: 10.12688/f1000research.9180.1. eCollection 2016.

Abstract

Circadian clock proteins form an autoregulatory feedback loop that is central to the endogenous generation and transmission of daily rhythms in behavior and physiology. Increasingly, circadian rhythms in clock gene expression are being reported in diverse tissues and brain regions that lie outside of the suprachiasmatic nucleus (SCN), the master circadian clock in mammals. For many of these extra-SCN rhythms, however, the region-specific implications are still emerging. In order to gain important insights into the potential behavioral, physiological, and psychological relevance of these daily oscillations, researchers have begun to focus on describing the neurochemical, hormonal, metabolic, and epigenetic contributions to the regulation of these rhythms. This review will highlight important sites and sources of circadian control within dopaminergic and striatal circuitries of the brain and will discuss potential implications for psychopathology and disease . For example, rhythms in clock gene expression in the dorsal striatum are sensitive to changes in dopamine release, which has potential implications for Parkinson's disease and drug addiction. Rhythms in the ventral striatum and limbic forebrain are sensitive to psychological and physical stressors, which may have implications for major depressive disorder. Collectively, a rich circadian tapestry has emerged that forces us to expand traditional views and to reconsider the psychopathological, behavioral, and physiological importance of these region-specific rhythms in brain areas that are not immediately linked with the regulation of circadian rhythms.

摘要

昼夜节律时钟蛋白形成一个自动调节反馈回路,这是行为和生理中日常节律的内源性产生和传递的核心。越来越多的研究报告称,在哺乳动物的主昼夜节律时钟——视交叉上核(SCN)之外的各种组织和脑区中,时钟基因表达存在昼夜节律。然而,对于许多这些SCN外的节律,其区域特异性影响仍在不断显现。为了深入了解这些日常振荡在行为、生理和心理方面的潜在相关性,研究人员已开始专注于描述神经化学、激素、代谢和表观遗传因素对这些节律调节的作用。本综述将重点介绍大脑多巴胺能和纹状体回路中昼夜节律控制的重要位点和来源,并将讨论其对精神病理学和疾病的潜在影响。例如,背侧纹状体中时钟基因表达的节律对多巴胺释放的变化敏感,这对帕金森病和药物成瘾具有潜在影响。腹侧纹状体和边缘前脑的节律对心理和身体应激源敏感,这可能对重度抑郁症有影响。总的来说,一幅丰富的昼夜节律图景已经浮现,这迫使我们扩展传统观点,并重新考虑这些在与昼夜节律调节没有直接联系的脑区中区域特异性节律在精神病理学、行为和生理方面的重要性。

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