Department of Clinical Research and Innovation (DRCI), Hôpital Foch, Suresnes, France.
Centre de Recherche Clinique, Grand Hôpital de l'Est Francilien (GHEF), Meaux, France.
Transl Psychiatry. 2020 Nov 16;10(1):400. doi: 10.1038/s41398-020-01086-9.
Intellectual abilities and their clinical presentations are extremely heterogeneous in autism spectrum disorder (ASD). The main causes of ASD remain unclear. ASD is frequently associated with sleep disorders. Biologic rhythms are complex systems interacting with the environment and controlling several physiological pathways, including brain development and behavioral processes. Recent findings have shown that the deregulation of the core clock neurodevelopmental signaling is correlated with ASD clinical presentation. One of the main pathways involved in developmental cognitive disorders is the canonical WNT/β-catenin pathway. Circadian clocks have a main role in some tissues by driving circadian expression of genes involved in physiologic and metabolic functions. In ASD, the increase of the canonical WNT/β-catenin pathway is enhancing by the dysregulation of circadian rhythms. ASD progression is associated with a major metabolic reprogramming, initiated by aberrant WNT/β-catenin pathway, the aerobic glycolysis. This review focuses on the interest of circadian rhythms dysregulation in metabolic reprogramming in ASD through the aberrant upregulation of the canonical WNT/β-catenin pathway.
自闭症谱系障碍（ASD）患者的智力能力及其临床表现存在极大的异质性。ASD 的主要病因仍不清楚。ASD 常与睡眠障碍有关。生物节律是与环境相互作用并控制包括大脑发育和行为过程在内的多种生理途径的复杂系统。最近的研究结果表明，核心时钟神经发育信号的失调与 ASD 的临床表现相关。参与发育认知障碍的主要途径之一是经典 WNT/β-连环蛋白途径。生物钟在某些组织中通过驱动与生理和代谢功能相关的基因的昼夜表达发挥主要作用。在 ASD 中，生物钟节律的失调会增强经典 WNT/β-连环蛋白途径的增加。ASD 的进展与由异常 WNT/β-连环蛋白途径引发的有氧糖酵解引起的主要代谢重编程有关。本综述重点讨论了通过异常上调经典 WNT/β-连环蛋白途径，生物钟节律失调在 ASD 代谢重编程中的作用。
