Narcolepsy in orexin knockout mice:: Molecular genetics of sleep regulation
Narcolepsy in orexin knockout mice:: Molecular genetics of sleep regulation
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DOI：
10.1016/s0092-8674(00)81973-x
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发表时间：
1999-08-20
期刊：
影响因子：
64.5
通讯作者：
Yanagisawa, M
中科院分区：
文献类型：
--
作者：
Chemelli, RM;Willie, JT;Yanagisawa, M
含有神经肽食欲素（下丘脑分泌素）的神经元仅位于下丘脑外侧，并将轴突发送到整个中枢神经系统的许多区域，包括与睡眠调节有关的主要细胞核。在这里，我们报告说，根据行为和脑电图标准，食欲素敲除小鼠表现出与人类嗜睡症患者以及 canarc-1 突变体惊人相似的表型 狗是唯一已知的嗜睡症单基因模型。此外，莫达非尼是一种作用机制不明确的抗发作性睡病药物，可激活含有食欲素的神经元。我们提出食欲素调节睡眠/清醒状态，而食欲素基因敲除小鼠是人类嗜睡症的模型，这种疾病的主要特征是快速眼动（REM）睡眠失调。
Neurons containing the neuropeptide orexin (hypocretin) are located exclusively in the lateral hypothalamus and send axons to numerous regions throughout the central nervous system, including the major nuclei implicated in sleep regulation, Here, we report that, by behavioral and electroencephalographic criteria, orexin knockout mice exhibit a phenotype strikingly similar to human narcolepsy patients, as well as canarc-1 mutant dogs, the only known monogenic model of narcolepsy. Moreover, modafinil, an anti-narcoleptic drug with ill-defined mechanisms of action, activates orexin-containing neurons. We propose that orexin regulates sleep/wakefulness states, and that orexin knockout mice are a model of human narcolepsy, a disorder characterized primarily by rapid eye movement (REM) sleep dysregulation.