When clocks go bad: neurobehavioural consequences of disrupted circadian timing.
When clocks go bad: neurobehavioural consequences of disrupted circadian timing.
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DOI：
10.1371/journal.pgen.1000040
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发表时间：
2008-05-30
期刊：
影响因子：
4.5
通讯作者：
Nolan, Patrick M.
中科院分区：
文献类型：
--
作者：
Barnard, Alun R.;Nolan, Patrick M.
在过去的十年中，在解开哺乳动物昼夜节律调节的细胞和分子基础方面的进展为我们提供了新的途径，通过这些途径，我们可以探索中枢神经系统疾病。可测量的昼夜输出参数的恶化，如睡眠/觉醒缺陷和循环激素水平失调，是大多数中枢神经系统疾病的常见特征。哺乳动物昼夜节律系统的核心是下丘脑视交叉上核内复杂的分子振荡。这些振荡可由来自环境的传入信号修改，并且集成信号随后被传送到远程中枢神经回路，其中特定的输出节律被调节。小鼠昼夜节律基因的突变可以干扰分子振荡和可测量的输出节律。此外，对这些突变体的系统分析表明，它们可以表达一系列异常行为表型，这些表型是中枢神经系统疾病的中间特征。此外，这些突变体对精神药物的反应表明，时钟基因可以改变大脑中许多关键的神经递质系统。这一证据导致了对精神疾病中时钟基因多态性的有希望的调查。初步迹象有利于昼夜节律基因对中枢神经系统疾病的贡献的系统调查。
Progress in unravelling the cellular and molecular basis of mammalian circadian regulation over the past decade has provided us with new avenues through which we can explore central nervous system disease. Deteriorations in measurable circadian output parameters, such as sleep/wake deficits and dysregulation of circulating hormone levels, are common features of most central nervous system disorders. At the core of the mammalian circadian system is a complex of molecular oscillations within the hypothalamic suprachiasmatic nucleus. These oscillations are modifiable by afferent signals from the environment, and integrated signals are subsequently conveyed to remote central neural circuits where specific output rhythms are regulated. Mutations in circadian genes in mice can disturb both molecular oscillations and measurable output rhythms. Moreover, systematic analysis of these mutants indicates that they can express an array of abnormal behavioural phenotypes that are intermediate signatures of central nervous system disorders. Furthermore, the response of these mutants to psychoactive drugs suggests that clock genes can modify a number of the brain’s critical neurotransmitter systems. This evidence has led to promising investigations into clock gene polymorphisms in psychiatric disease. Preliminary indications favour the systematic investigation of the contribution of circadian genes to central nervous system disease.
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