Korshunov Kirill S, Blakemore Laura J, Trombley Paul Q
Program in Neuroscience, Florida State University,Tallahassee, FL, USA.
Department of Biological Science, Florida State University,Tallahassee, FL, USA.
Front Cell Neurosci. 2017 Apr 3;11:91. doi: 10.3389/fncel.2017.00091. eCollection 2017.
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.
昼夜节律是调节许多生物过程的每日节律——从基因转录到行为——而这些节律的破坏会导致无数健康风险。昼夜节律受光线影响，其24小时振荡由一个核心分子反馈环维持，该反馈环由典型的昼夜节律（“时钟”）基因和蛋白质组成。不同的调节因子有助于维持这些基因和蛋白质的适当节律性，一种新兴的调节因子是多巴胺。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，在这些区域中的一些区域，它调节时钟基因并受其调节。因此，多巴胺很可能对维持这五个脑区适当节律性的机制至关重要。本综述讨论了展示不同多巴胺能机制的研究，这些机制可能与这些脑区昼夜节律的调节有关。这些机制包括多巴胺和多巴胺受体活性如何直接和间接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每日神经元兴奋性，以及多巴胺的释放和作用如何由低通和高通滤波器控制。由于本综述中描述的多巴胺神经元还释放抑制性神经递质GABA，而GABA会影响视网膜中时钟蛋白的表达，因此我们讨论了探索GABA如何可能促成多巴胺神经元对昼夜节律作用的文章。最后，为了了解多巴胺神经元功能丧失如何影响昼夜节律，我们综述了将神经退行性疾病帕金森病与这五个脑区昼夜节律破坏联系起来的研究。本综述的目的是总结越来越多的证据，表明多巴胺在此处讨论的脑区中直接或间接参与调节昼夜节律。认识到多巴胺对昼夜节律影响的证据不断增加，可能会带来新的治疗方法，包括旨在缓解昼夜节律紊乱各种症状的药物。
