Division of Neurology, Department of Medicine, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, ON, Canada.
Handb Clin Neurol. 2021;179:271-284. doi: 10.1016/B978-0-12-819975-6.00017-0.
Diurnal and seasonal rhythms influence many aspects of human physiology including brain function. Moreover, altered diurnal and seasonal behavioral and physiological rhythms have been linked to Alzheimer's disease and related dementias (ADRD). Understanding the molecular basis for these links may lead to identification of novel targets to mitigate the negative impact of normal and abnormal diurnal and seasonal rhythms on ADRD or to alleviate the adverse consequences of ADRD on normal diurnal and seasonal rhythms. Diurnally and seasonally rhythmic gene expression and epigenetic modification in the human neocortex may be a key mechanism underlying these links. This chapter will first review the observed epidemiological links between normal and abnormal diurnal and seasonal rhythmicity, cognitive impairment, and ADRD. Then it will review normal diurnal and seasonal rhythms of brain epigenetic modification and gene expression in model organisms. Finally, it will review evidence for diurnal and seasonal rhythms of epigenetic modification and gene expression the human brain in aging, Alzheimer's disease, and other brain disorders.
昼夜节律和季节节律会影响人类生理的许多方面，包括大脑功能。此外，昼夜和季节性行为及生理节律的改变与阿尔茨海默病及相关痴呆症（ADRD）有关。了解这些关联的分子基础，可能有助于确定新的靶点，减轻正常和异常昼夜及季节节律对 ADRD 的负面影响，或减轻 ADRD 对正常昼夜及季节节律的不利影响。人类大脑新皮质中昼夜节律和季节性基因表达和表观遗传修饰可能是这些关联的关键机制。本章首先将回顾正常和异常昼夜及季节性节律、认知障碍和 ADRD 之间观察到的流行病学关联。然后将综述模型生物中大脑表观遗传修饰和基因表达的正常昼夜和季节性节律。最后，将综述衰老、阿尔茨海默病和其他脑部疾病中人类大脑的表观遗传修饰和基因表达的昼夜和季节性节律的证据。
