Department of Human Genetics, National Institute of Mental Health and Neurosciences, Hosur Road, Bangalore, 560029, Karnataka, India.
Department of Child and Adolescent Psychiatry, National Institute of Mental Health and Neurosciences, Hosur Road, Bangalore, 560029, Karnataka, India.
Rev Neurosci. 2021 May 28;33(1):93-109. doi: 10.1515/revneuro-2021-0022. Print 2022 Jan 27.
Circadian rhythms in most living organisms are regulated by light and synchronized to an endogenous biological clock. The circadian clock machinery is also critically involved in regulating and fine-tuning neurodevelopmental processes. Circadian disruption during embryonic development can impair crucial phases of neurodevelopment. This can contribute to neurodevelopmental disorders like autism spectrum disorder (ASD) in the offspring. Increasing evidence from studies showing abnormalities in sleep and melatonin as well as genetic and epigenetic changes in the core elements of the circadian pathway indicate a pivotal role of circadian disruption in ASD. However, the underlying mechanistic basis through which the circadian pathways influence the risk and progression of ASD are yet to be fully discerned. Well-recognized mechanistic pathways in ASD include altered immune-inflammatory, nitro oxidative stress, neurotransmission and synaptic plasticity, and metabolic pathways. Notably, all these pathways are under the control of the circadian clock. It is thus likely that a disrupted circadian clock will affect the functioning of these pathways. Herein, we highlight the possible mechanisms through which aberrations in the circadian clock might affect immune-inflammatory, nitro-oxidative, metabolic pathways, and neurotransmission, thereby driving the neurobiological sequelae leading to ASD.
大多数生物的昼夜节律受光调节，并与内源性生物钟同步。生物钟机制也在调节和微调神经发育过程中起着关键作用。胚胎发育过程中的昼夜节律紊乱会损害神经发育的关键阶段。这可能导致后代出现自闭症谱系障碍 (ASD) 等神经发育障碍。越来越多的研究表明，睡眠和褪黑素异常，以及昼夜节律途径核心元件的遗传和表观遗传变化，都表明昼夜节律紊乱在 ASD 中起着关键作用。然而，昼夜节律途径影响 ASD 风险和进展的潜在机制基础尚未完全阐明。ASD 中公认的机制途径包括免疫炎症改变、氮氧化应激、神经传递和突触可塑性以及代谢途径。值得注意的是，所有这些途径都受生物钟的控制。因此，昼夜节律紊乱很可能会影响这些途径的功能。在此，我们强调了昼夜节律紊乱可能通过哪些机制影响免疫炎症、氮氧化应激、代谢途径和神经传递，从而导致导致 ASD 的神经生物学后果。
