Narcolepsy in orexin Knockout Mice Molecular Genetics of Sleep Regulation
نویسندگان
چکیده
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.
منابع مشابه
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Mochizuki, Takatoshi, Elizabeth B. Klerman, Takeshi Sakurai, and Thomas E. Scammell. Elevated body temperature during sleep in orexin knockout mice. Am J Physiol Regul Integr Comp Physiol 291: R533–R540, 2006. First published March 23, 2006; doi:10.1152/ajpregu.00887.2005.— Core body temperature (Tb) is influenced by many physiological factors, including behavioral state, locomotor activity, an...
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Core body temperature (Tb) is influenced by many physiological factors, including behavioral state, locomotor activity, and biological rhythms. To determine the relative roles of these factors, we examined Tb in orexin knockout (KO) mice, which have a narcolepsy-like phenotype with severe sleep-wake fragmentation. Because orexin is released during wakefulness and is thought to promote heat prod...
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ورودعنوان ژورنال:
- Cell
دوره 98 شماره
صفحات -
تاریخ انتشار 1999