Circadian rhythms are approximate 24-hour rhythms present in nearly all aspects of human physiology, including proper brain function. These rhythms are produced at the cellular level through a transcriptional-translational feedback loop known as the molecular clock. Diurnal variation in gene expression has been demonstrated in brain tissue from multiple species, including humans, in both cortical and subcortical regions. Interestingly, these rhythms in gene expression have been shown to be disrupted across psychiatric disorders and may be implicated in their underlying pathophysiology. However, little is known regarding molecular rhythms in specific cell types in the brain and how they might be involved in psychiatric disease. Although glial cells (e.g., astrocytes, microglia, and oligodendrocytes) have been historically understudied compared to neurons, evidence of the molecular clock is found within each of these cell subtypes. Here, we review the current literature, which suggests that molecular rhythmicity is essential to functional physiologic outputs from each glial subtype. Furthermore, disrupted molecular rhythms within these cells and the resultant functional deficits may be relevant to specific phenotypes across psychiatric illnesses. Given that circadian rhythm disruptions have been so integrally tied to psychiatric disease, the molecular mechanisms governing these associations could represent exciting new avenues for future research and potential novel pharmacologic targets for treatment.

中文翻译：

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胶质细胞中的分子节律：对大脑健康的重要性和与精神疾病的相关性


昼夜节律是大约 24 小时的节律，几乎存在于人类生理学的所有方面，包括适当的大脑功能。这些节律是通过称为分子钟的转录-翻译反馈回路在细胞水平上产生的。基因表达的昼夜变化已在包括人类在内的多个物种的脑组织中得到证实，包括皮层和皮层下区域。有趣的是，基因表达的这些节律已被证明在精神疾病中被破坏，并且可能与它们的潜在病理生理学有关。然而，关于大脑中特定细胞类型的分子节律以及它们如何参与精神疾病，人们知之甚少。尽管与神经元相比，神经胶质细胞（例如星形胶质细胞、小胶质细胞和少突胶质细胞）历来研究不足，但在这些细胞亚型中的每一种中都可以找到分子钟的证据。在这里，我们回顾了当前的文献，这些文献表明分子节律性对于每种神经胶质细胞亚型的功能性生理输出至关重要。此外，这些细胞内分子节律的破坏和由此产生的功能缺陷可能与精神疾病的特定表型有关。鉴于昼夜节律紊乱与精神疾病有着如此紧密的联系，控制这些关联的分子机制可能代表令人兴奋的未来研究和潜在的新治疗药理学靶点的新途径。