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生物钟建模:从分子机制到生理紊乱

Modeling the circadian clock: from molecular mechanism to physiological disorders.

作者信息

Leloup Jean-Christophe, Goldbeter Albert

机构信息

Faculté des Sciences, Université Libre de Bruxelles, Belgium.

出版信息

Bioessays. 2008 Jun;30(6):590-600. doi: 10.1002/bies.20762.

Abstract

Based on genetic and biochemical advances on the molecular mechanism of circadian rhythms, a computational model for the mammalian circadian clock is used to examine the dynamical bases of circadian-clock-related physiological disorders in humans. Entrainment by the light-dark cycle with a phase advance or a phase delay is associated with the Familial advanced sleep phase syndrome (FASPS) or the Delayed sleep phase syndrome (DSPS), respectively. Lack of entrainment corresponding to the occurrence of quasiperiodic oscillations with or without phase jump can be associated with the non-24 h sleep-wake syndrome. In the close vicinity of the entrainment domain, the model uncovers the possibility of infradian oscillations of very long period. Perturbation in the form of chronic jet lag, as used in mice, prevents entrainment of the circadian clock and results in chaotic or quasiperiodic oscillations. It is important to clarify the conditions for entrainment and for its failure because dysfunctions of the circadian clock may lead to physiological disorders, which pertain not only to the sleep-wake cycle but also to mood and cancer.

摘要

基于昼夜节律分子机制在遗传学和生物化学方面的进展,一个用于哺乳动物生物钟的计算模型被用来研究人类与生物钟相关的生理紊乱的动力学基础。明暗周期的相位提前或相位延迟诱导分别与家族性早睡相位综合征(FASPS)或晚睡相位综合征(DSPS)相关。对应于有或没有相位跳跃的准周期振荡的发生而缺乏诱导可能与非24小时睡眠-觉醒综合征相关。在诱导域的紧邻区域,该模型揭示了极长周期的次昼夜振荡的可能性。如在小鼠中所使用的,以慢性时差的形式进行扰动会阻止生物钟的诱导,并导致混沌或准周期振荡。阐明诱导及其失败的条件很重要,因为生物钟功能障碍可能导致生理紊乱,这不仅涉及睡眠-觉醒周期,还涉及情绪和癌症。

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