Melatonin is required for the circadian regulation of sleep.
Melatonin is required for the circadian regulation of sleep.
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DOI：
10.1016/j.neuron.2015.02.016
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发表时间：
2015-03-18
期刊：
影响因子：
16.2
通讯作者：
Prober DA
中科院分区：
文献类型：
--
作者：
Gandhi AV;Mosser EA;Oikonomou G;Prober DA
睡眠是一种进化上保守的行为状态，人们对其调控知之甚少。一个经典的模型假设睡眠是由体内平衡和昼夜节律机制调节的。有几个因素与调节睡眠的稳态调节有关，但昼夜节律机制背后的分子尚不清楚。在这里，我们使用由于芳基烷基胺n -乙酰转移酶2 （aanat2）突变而缺乏褪黑激素的动物来证明褪黑激素是斑马鱼睡眠昼夜节律调节所必需的。维持在光照/黑暗条件下的aanat2突变体在夜间睡眠显著减少，并且在自由运行条件下睡眠的昼夜节律调节被取消。我们发现褪黑激素促进生物钟下游的睡眠，因为它不是启动或维持昼夜节律所必需的。此外，我们提供的证据表明，褪黑激素可能部分通过促进腺苷信号传导来诱导睡眠，从而潜在地将昼夜节律和睡眠的稳态控制联系起来。
Sleep is an evolutionarily conserved behavioral state whose regulation is poorly understood. A classical model posits that sleep is regulated by homeostatic and circadian mechanisms. Several factors have been implicated in mediating the homeostatic regulation of sleep, but molecules underlying the circadian mechanism are unknown. Here we use animals lacking melatonin due to mutation of arylalkylamine N-acetyltransferase 2 (aanat2) to show that melatonin is required for circadian regulation of sleep in zebrafish. Sleep is dramatically reduced at night in aanat2 mutants maintained in light/dark conditions, and the circadian regulation of sleep is abolished in free-running conditions. We find that melatonin promotes sleep downstream of the circadian clock as it is not required to initiate or maintain circadian rhythms. Additionally, we provide evidence that melatonin may induce sleep in part by promoting adenosine signaling, thus potentially linking circadian and homeostatic control of sleep.