Parmalee Nancy L, Aschner Michael
Albert Einstein College of Medicine, Department of Molecular Pharmacology, 1300 Morris Park Avenue, Bronx, New York, USA.
Adv Neurotoxicol. 2017;1:119-130. doi: 10.1016/bs.ant.2017.07.003. Epub 2017 Sep 1.
Circadian rhythms describe the behavioral and physiological changes that occur in living organisms in order to attune to a 24 hour cycle of day and night. The most striking aspect of circadian function is the sleep-wake cycle, however many other physiological processes are regulated in 24 hour oscillations, including blood pressure, body temperature, appetite, urine production, and the transcription and translation of thousands of circadian dependent genes. Circadian disruption and sleep disorders are strongly connected to neurodegenerative diseases including Parkinson's disease, Alzheimer's disease, and Huntington's disease as well as others. Metal exposures have been implicated in neurodegenerative diseases, in some cases involving metals that are essential micronutrients but are toxic at high levels of exposure (such as manganese, copper, and zinc), and in other cases involving metals that have no biological role but are toxic to living systems (such as lead, mercury, and aluminum). In this review, we examine the evidence for circadian and sleep disorders with exposures to these metals and review the literature for possible mechanisms. We suggest that giving the aging population, the prevalence of environmental exposures to metals, and the increasing prevalence of neurodegenerative disease in the aged, more research into the mechanisms of circadian disruption subsequent to metal exposures is warranted.
昼夜节律描述了生物体中发生的行为和生理变化,以便与昼夜24小时周期相协调。昼夜节律功能最显著的方面是睡眠-觉醒周期,然而许多其他生理过程也以24小时振荡的方式受到调节,包括血压、体温、食欲、尿液生成以及数千种昼夜节律相关基因的转录和翻译。昼夜节律紊乱和睡眠障碍与包括帕金森病、阿尔茨海默病和亨廷顿病等在内的神经退行性疾病以及其他疾病密切相关。金属暴露与神经退行性疾病有关,在某些情况下涉及作为必需微量营养素但在高暴露水平下有毒的金属(如锰、铜和锌),而在其他情况下涉及对生物系统有毒但无生物学作用的金属(如铅、汞和铝)。在本综述中,我们研究了这些金属暴露导致昼夜节律和睡眠障碍的证据,并综述了可能机制的文献。我们认为,鉴于老年人口、环境中金属暴露的普遍性以及老年人中神经退行性疾病患病率的上升,有必要对金属暴露后昼夜节律紊乱的机制进行更多研究。