Division of Neurobiology, Medical Research Council Laboratory of Molecular Biology, Cambridge, United Kingdom; email:
UK Dementia Research Institute and Department of Brain Sciences, Imperial College London, London, United Kingdom.
Annu Rev Neurosci. 2023 Jul 10;46:123-143. doi: 10.1146/annurev-neuro-100322-112249. Epub 2023 Mar 28.
This review explores the interface between circadian timekeeping and the regulation of brain function by astrocytes. Although astrocytes regulate neuronal activity across many time domains, their cell-autonomous circadian clocks exert a particular role in controlling longer-term oscillations of brain function: the maintenance of sleep states and the circadian ordering of sleep and wakefulness. This is most evident in the central circadian pacemaker, the suprachiasmatic nucleus, where the molecular clock of astrocytes suffices to drive daily cycles of neuronal activity and behavior. In Alzheimer's disease, sleep impairments accompany cognitive decline. In mouse models of the disease, circadian disturbances accelerate astroglial activation and other brain pathologies, suggesting that daily functions in astrocytes protect neuronal homeostasis. In brain cancer, treatment in the morning has been associated with prolonged survival, and gliomas have daily rhythms in gene expression and drug sensitivity. Thus, circadian time is fast becoming critical to elucidating reciprocal astrocytic-neuronal interactions in health and disease.
这篇综述探讨了生物钟与星形胶质细胞调节大脑功能之间的界面。星形胶质细胞在许多时间域中调节神经元活动,但其细胞自主的生物钟在控制大脑功能的长期振荡方面发挥着特殊作用:维持睡眠状态以及睡眠和觉醒的昼夜节律。这在中枢生物钟起搏器——视交叉上核中最为明显,星形胶质细胞的分子钟足以驱动神经元活动和行为的每日周期。在阿尔茨海默病中,睡眠障碍伴随着认知能力下降。在该疾病的小鼠模型中,昼夜节律紊乱会加速星形胶质细胞的激活和其他脑部病变,表明星形胶质细胞的日常功能可保护神经元的内稳态。在脑癌中,早晨进行治疗与延长生存期有关,而神经胶质瘤的基因表达和药物敏感性存在每日节律。因此,昼夜节律时间对于阐明健康和疾病中星形胶质细胞与神经元的相互作用变得至关重要。