The Steroid Molting Hormone Ecdysone Regulates Sleep in Adult Drosophila melanogaster
The Steroid Molting Hormone Ecdysone Regulates Sleep in Adult Drosophila melanogaster
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DOI：
10.1534/genetics.110.114587
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发表时间：
2010-05-01
期刊：
影响因子：
3.3
通讯作者：
Kitamoto, Toshihiro
中科院分区：
文献类型：
--
作者：
Ishimoto, Hiroshi;Kitamoto, Toshihiro
蜕皮酮是昆虫体内主要的类固醇激素，通过其活性代谢物20-羟基蜕皮酮(20E)在幼虫蜕皮、变态等发育过程中发挥重要作用。虽然蜕皮激素在男性和女性的一生中都存在，但它在成年生理中的作用仍然很大程度上是未知的。在这项研究中，我们证明了在成人中，蜕皮激素介导的信号与睡眠和清醒的生理状态之间的转换密切相关。首先，给成年果蝇注射20E以一种剂量依赖的方式促进睡眠，而且它主要是通过改变睡眠时间和醒来次数来实现的，而不影响清醒时的活动。其次，蜕皮激素合成的突变体表现出“短眠表型”，在成体阶段给予20E可以缓解这种情况。第三，核蜕皮激素受体突变体显示睡眠减少，在成年蘑菇体中野生型蜕皮激素受体有条件地过度表达导致同型特异性睡眠增加。最后，内源性蜕皮激素水平在睡眠剥夺后增加，而蜕皮激素信号缺陷突变体几乎没有表现出睡眠反弹，这表明蜕皮激素参与了动态平衡睡眠调节。鉴于最近的发现，嗜睡是线虫线虫幼虫阶段向幼虫阶段过渡的时期，是一种类似睡眠的状态，我们的结果表明，睡眠在功能和机械上与发育过程中遗传编程的静止行为状态有关。
Ecdysone is the major steroid hormone in insects and plays essential roles in coordinating developmental transitions such as larval molting and metamorphosis through its active metabolite 20-hydroxyecdysone (20E). Although ecdysone is present throughout life in both males and females, its functions in adult physiology remain largely unknown. In this study we demonstrate that ecdysone-mediated signaling in the adult is intimately involved in transitions between the physiological states of sleep and wakefulness. First, administering 20E to adult Drosophila melanogaster promoted sleep in a dose-dependent manner, and it did so primarily by altering the length of sleep and wake bouts without affecting waking activity. Second, mutants for ecdysone synthesis displayed the "short-sleep phenotype," and this was alleviated by administering 20E at the adult stage. Third, mutants for nuclear ecdysone receptors showed reduced sleep, and conditional overexpression of wild-type ecdysone receptors in the adult mushroom bodies resulted in an isoform-specific increase in sleep. Finally, endogenous ecdysone levels increased after sleep deprivation, and mutants defective for ecdysone signaling displayed little sleep rebound, suggesting that ecdysone is involved in homeostatic sleep regulation. In light of the recent finding that lethargus-a period at larval-stage transitions in the nematode worm Caenorhabditis elegans-is a sleep-like state, our results suggest that sleep is functionally and mechanistically linked to a genetically programmed, quiescent behavioral state during development.