Regulation of Sleep by Insulin-like Peptide System in Drosophila melanogaster

Regulation of Sleep by Insulin-like Peptide System in Drosophila melanogaster
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果蝇胰岛素样肽系统对睡眠的调节。

DOI：
10.5665/sleep.4816
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发表时间：
2015-07-01
期刊：
SLEEP
影响因子：
5.6
通讯作者：
Zhao, Zhangwu
Zhao, Zhangwu
中科院分区：
医学2区
文献类型：
--
作者：
Cong, Xiaona;Wang, Haili;Zhao, Zhangwu

文献摘要

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学习目标 大多数生物体都有行为和生理昼夜节律，由内源性时钟控制。尽管遗传分析揭示了生物钟的细胞内机制，但该生物钟如何传达其时间信息以产生系统调节的方式仍然很大程度上未知。 设计 使用果蝇活动监测系统（DAMS）监测器在 12 小时光照：12 ​​小时黑暗周期和持续黑暗（DD）下测量睡眠行为，并将 5 分钟没有记录活动定义为一次睡眠。 结果 在这里，我们证明果蝇胰岛素样肽（DILP）及其受体（DInR）调节睡眠行为。除dilp4突变体外，七种dilps的所有突变体及其受体突变体均表现出总睡眠减少，而神经系统中DILP和DInR的上调导致睡眠增加。组织学分析发现了四个先前未识别的表达 DILP 的神经元：D1、P1、L1 和 L2，其中 L1 和 L2 属于分别调节不同睡眠时间的 LNd 和 LNv 时钟神经元。此外，当果蝇禁食时，dilp2水平显着降低，这与之前关于饥饿抑制睡眠的报道一致，进一步表明dilp系统参与睡眠调节。 结论 综上所述，结果表明果蝇胰岛素样肽系统是睡眠的重要调节剂。
STUDY OBJECTIVES Most organisms have behavioral and physiological circadian rhythms, which are controlled by an endogenous clock. Although genetic analysis has revealed the intracellular mechanism of the circadian clock, the manner in which this clock communicates its temporal information to produce systemic regulation is still largely unknown. DESIGN Sleep behavior was measured using the Drosophila Activity Monitoring System (DAMS) monitor under a 12 h light:12 h dark cycle and constant darkness (DD), and 5 min without recorded activity were defined as a bout of sleep. RESULTS Here we show that Drosophila insulin-like peptides (DILPs) and their receptor (DInR) regulate sleep behavior. All mutants of the seven dilps and the mutant of their receptor exhibit decreases of total sleep except dilp4 mutants, whereas upregulation of DILP and DInR in the nervous system led to increased sleep. Histological analysis identified four previously unidentified neurons expressing DILP: D1, P1, L1, and L2, of which L1 and L2 belong to the LNd and LNv clock neurons that separately regulate different times of sleep. In addition, dilp2 levels significantly decrease when flies were fasted, which is consistent with a previous report that starvation inhibits sleep, further indicating that the dilp system is involved in sleep regulation. CONCLUSION Taken together, the results indicate that the Drosophila insulin-like peptide system is a crucial regulator of sleep.