Geoffray M-M, Nicolas A, Speranza M, Georgieff N
Department of Child and Adolescent Psychiatry, Centre Hospitalier le Vinatier, Lyon, France.
Unité d'exploration Hypnologique, Service Hospitalo-Universitaire de Psychiatrie, Centre Hospitalier spécialisé Le Vinatier, Lyon, France.
J Physiol Paris. 2016 Nov;110(4 Pt B):434-438. doi: 10.1016/j.jphysparis.2017.06.002. Epub 2017 Jun 20.
Autism Spectrum Disorder (ASD) is a frequent neurodevelopmental disorder. ASD is probably the result of intricate interactions between genes and environment altering progressively the development of brain structures and functions. Circadian rhythms are a complex intrinsic timing system composed of almost as many clocks as there are body cells. They regulate a variety of physiological and behavioral processes such as the sleep-wake rhythm. ASD is often associated with sleep disorders and low levels of melatonin. This first point raises the hypothesis that circadian rhythms could have an implication in ASD etiology. Moreover, circadian rhythms are generated by auto-regulatory genetic feedback loops, driven by transcription factors CLOCK and BMAL1, who drive transcription daily patterns of a wide number of clock-controlled genes (CCGs) in different cellular contexts across tissues. Among these, are some CCGs coding for synapses molecules associated to ASD susceptibility. Furthermore, evidence emerges about circadian rhythms control of time brain development processes.
自闭症谱系障碍（ASD）是一种常见的神经发育障碍。ASD可能是基因与环境之间复杂相互作用的结果，这种相互作用逐渐改变大脑结构和功能的发育。昼夜节律是一个复杂的内在计时系统，其组成的时钟数量几乎与身体细胞数量一样多。它们调节各种生理和行为过程，如睡眠-觉醒节律。ASD常与睡眠障碍和褪黑素水平低有关。这第一点提出了昼夜节律可能与ASD病因有关的假设。此外，昼夜节律由自动调节的基因反馈回路产生，由转录因子CLOCK和BMAL1驱动，它们在不同组织的不同细胞环境中驱动大量生物钟控制基因（CCG）的每日转录模式。其中，一些CCG编码与ASD易感性相关的突触分子。此外，有证据表明昼夜节律对大脑发育过程具有时间控制作用。
