Strong resetting of the mammalian clock by constant light followed by constant darkness.
Strong resetting of the mammalian clock by constant light followed by constant darkness.
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DOI：
10.1523/jneurosci.2191-08.2008
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发表时间：
2008-11-12
期刊：
影响因子：
--
通讯作者：
Lee C
中科院分区：
文献类型：
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作者：
Chen R;Seo DO;Bell E;von Gall C;Lee C
哺乳动物视交叉上核（SCN）中的分子生物钟调节运动活动节律以及外周组织的时钟。恒定光（LL）可以通过使SCN中的时钟细胞不同步来诱导行为和生理心律失常。我们通过探测分子时钟和测量小鼠从LL转移到恒定黑暗（DD）的行为来研究紊乱的时钟细胞如何重新同步。从DD开始，LL中中断的昼夜运动活动节律再次变得有节奏，并且DD中节律的起始阶段是特定的，而不是随机的，这表明不同步的时钟细胞通过L:D转换以非常规的方式迅速重置。通过测量mPERIOD蛋白节律，我们发现SCN和外周组织时钟很快又与行为节律同步。我们认为这种重置机制可能不同于传统的相移，后者涉及周期基因的光诱导。利用我们的功能见解，我们可以通过15小时的LL治疗将运动活动节律的昼夜节律改变12小时：本质上是通过单个光脉冲产生相位逆转，这一壮举以前未在野生型小鼠中报道过，具有潜在的临床应用价值。
The mammalian molecular circadian clock in the suprachiasmatic nuclei (SCN) regulates locomotor activity rhythms as well as clocks in peripheral tissues. Constant light (LL) can induce behavioral and physiological arrhythmicity, by desynchronizing clock cells in the SCN. We examined how the disordered clock cells resynchronize by probing the molecular clock and measuring behavior in mice transferred from LL to constant darkness (DD). The circadian locomotor activity rhythms disrupted in LL become robustly rhythmic again from the beginning of DD, and the starting phase of the rhythm in DD is specific, not random, suggesting that the desynchronized clock cells are quickly reset in an unconventional manner by the L:D transition. By measuring mPERIOD protein rhythms, we showed that the SCN and peripheral tissue clocks quickly become rhythmic again in phase with the behavioral rhythms. We propose that this resetting mechanism may be different from conventional phase shifting, which involves light-induction of Period genes. Using our functional insights, we could shift the circadian phase of locomotor activity rhythms by 12 hours using a 15-hour LL treatment: essentially producing phase reversal by a single light pulse, a feat that has not been reported previously in wild-type mice and that has potential clinical utility.