Dopamine: A Modulator of Circadian Rhythms in the Central Nervous System.
Dopamine: A Modulator of Circadian Rhythms in the Central Nervous System.
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DOI：
10.3389/fncel.2017.00091
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发表时间：
2017
影响因子：
5.3
通讯作者：
Trombley PQ
中科院分区：
文献类型：
--
作者：
Korshunov KS;Blakemore LJ;Trombley PQ
昼夜节律是调节许多生物过程的日常节律--从基因转录到行为--这些节律的中断可能会导致无数的健康风险。昼夜节律受光的影响，其24小时的振荡由标准的昼夜节律基因和蛋白质组成的核心分子反馈环路维持。不同的调节剂有助于维持这些基因和蛋白质的适当节律性，其中一个新出现的调节剂是多巴胺。多巴胺已被证明在视网膜、嗅球、纹状体、中脑和下丘脑具有类似昼夜节律的活动，在那里它调节其中一些区域的时钟基因，并受其调节。因此，多巴胺很可能是维持这五个大脑区域适当节律性的机制所必需的。这篇综述讨论了显示不同的多巴胺能机制的研究，这些机制可能与这些大脑区域的昼夜节律的调节有关。机制包括多巴胺和多巴胺受体的活动如何直接和间接地影响时钟基因和蛋白质，多巴胺与缝隙连接的相互作用如何影响日常神经元的兴奋性，以及多巴胺的释放和效应如何通过低通和高通过滤器来调节。由于本文中描述的多巴胺神经元还释放抑制性神经递质GABA，该神经递质影响视网膜中时钟蛋白的表达，因此我们讨论了GABA如何参与多巴胺神经元对昼夜节律的作用的文章。最后，为了了解多巴胺神经元功能的丧失如何影响昼夜节律，我们回顾了将神经退行性疾病帕金森病与这五个大脑区域的昼夜节律中断联系起来的研究。这篇综述的目的是总结越来越多的证据表明，多巴胺直接或间接地参与调节这里讨论的大脑区域的昼夜节律。对多巴胺对昼夜节律影响的越来越多的证据的评价可能会导致新的治疗方法，包括旨在缓解昼夜节律紊乱的各种症状的药物。
Circadian rhythms are daily rhythms that regulate many biological processes – from gene transcription to behavior – and a disruption of these rhythms can lead to a myriad of health risks. Circadian rhythms are entrained by light, and their 24-h oscillation is maintained by a core molecular feedback loop composed of canonical circadian (“clock”) genes and proteins. Different modulators help to maintain the proper rhythmicity of these genes and proteins, and one emerging modulator is dopamine. Dopamine has been shown to have circadian-like activities in the retina, olfactory bulb, striatum, midbrain, and hypothalamus, where it regulates, and is regulated by, clock genes in some of these areas. Thus, it is likely that dopamine is essential to mechanisms that maintain proper rhythmicity of these five brain areas. This review discusses studies that showcase different dopaminergic mechanisms that may be involved with the regulation of these brain areas’ circadian rhythms. Mechanisms include how dopamine and dopamine receptor activity directly and indirectly influence clock genes and proteins, how dopamine’s interactions with gap junctions influence daily neuronal excitability, and how dopamine’s release and effects are gated by low- and high-pass filters. Because the dopamine neurons described in this review also release the inhibitory neurotransmitter GABA which influences clock protein expression in the retina, we discuss articles that explore how GABA may contribute to the actions of dopamine neurons on circadian rhythms. Finally, to understand how the loss of function of dopamine neurons could influence circadian rhythms, we review studies linking the neurodegenerative disease Parkinson’s Disease to disruptions of circadian rhythms in these five brain areas. The purpose of this review is to summarize growing evidence that dopamine is involved in regulating circadian rhythms, either directly or indirectly, in the brain areas discussed here. An appreciation of the growing evidence of dopamine’s influence on circadian rhythms may lead to new treatments including pharmacological agents directed at alleviating the various symptoms of circadian rhythm disruption.