Rapid down-regulation of mammalian Period genes during behavioral resetting of the circadian clock
Rapid down-regulation of mammalian Period genes during behavioral resetting of the circadian clock
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DOI：
10.1073/pnas.96.26.15211
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发表时间：
1999-12-21
影响因子：
11.1
通讯作者：
Hastings, MH
中科院分区：
文献类型：
--
作者：
Maywood, ES;Mrosovsky, N;Hastings, MH
生物钟在调节生理和行为方面的普遍作用被广泛认识，它们的适应性价值在于它们能够受到环境线索的影响，从而使内部昼夜节律是太阳时间的可靠预测因子。在哺乳动物中，光和非光行为线索都可以携带下丘脑视交叉上核(SCN)的主振荡器。然而，尽管在昼夜期间，光可以使时钟提前或延迟，但行为事件会在主观的白天触发相位提前，此时时钟对光不敏感。最近在哺乳动物中发现了周期(PER)基因，这是编码果蝇昼夜节律的核心元件dPERE的同源物，现在提供了在分子水平上解释昼夜节律和夹带的机会。在小鼠中，mPer1和mPer2在SCN中的表达是有节律性的，并且受光的强烈上调，而且，mRNA和蛋白质周期之间的时间关系与基于转录/翻译反馈环的时钟一致。在这里，我们描述了叙利亚仓鼠SCN中PER1和PER2的昼夜振荡，表明PER1蛋白和mRNA周期再次以一种与负反馈振荡器一致的方式运行。此外，我们还证明了非光重置与光的作用相反：显著下调这些基因的表达。它们对非光重置信号的敏感性支持了它们作为昼夜节律振荡器核心元件的提议。此外，这项研究在分子水平上解释了光和非光线索对时钟的对比但汇聚的影响。
The pervasive role of circadian clocks in regulating physiology and behavior is widely recognized, Their adaptive value is their ability to be entrained by environmental cues such that the internal circadian phase is a reliable predictor of solar time, In mammals, both light and nonphotic behavioral cues can entrain the principal oscillator of the hypothalamic suprachiasmatic nuclei (SCN). However, although light can advance or delay the clock during circadian night, behavioral events trigger phase advances during the subjective day, when the clock is insensitive to light. The recent identification of Period (Per) genes in mammals, homologues of dperiod, which encodes a core element of the circadian clockwork in Drosophila, now provides the opportunity to explain circadian timing and entrainment at a molecular level. In mice, expression of mPer1 and mPer2 in the SCN is rhythmic and acutely up-regulated by light, Moreover, the temporal relations between mRNA and protein cycles are consistent with a clock based on a transcriptional/translational feedback loop. Here we describe circadian oscillations of Per1 and Per2 in the SCN of the Syrian hamster, showing that PER1 protein and mRNA cycles again behave in a manner consistent with a negative-feedback oscillator. Furthermore, we demonstrate that nonphotic resetting has the opposite effect to light: acutely down-regulating these genes. Their sensitivity to nonphotic resetting cues supports their proposed role as core elements of the circadian oscillator. Moreover, this study provides an explanation at the molecular level for the contrasting but convergent effects of photic and nonphotic cues on the clock.