To Eat or to Sleep? Orexin in the Regulation of Feeding and Wakefulness

Annual Review of Neuroscience - Tập 24 Số 1 - Trang 429-458 - 2001
Jon T. Willie1,2,3,4, Richard M. Chemelli1,2,3,4, Christopher M. Sinton1,2,3,4, Masashi Yanagisawa1,2,3,4
1Department of Molecular Genetics University of Texas Southwestern Medical Center at Dallas Dallas, Texas 75390-9050;
2Department of Pediatrics University of Texas Southwestern Medical Center at Dallas Dallas, Texas 75390-9050;
3Department of Psychiatry University of Texas Southwestern Medical Center at Dallas Dallas, Texas 75390-9050;
4Howard Hughes Medical Institute, University of Texas Southwestern Medical Center at Dallas Dallas, Texas 75390-9050;

Tóm tắt

▪ Abstract  Orexin-A and orexin-B are neuropeptides originally identified as endogenous ligands for two orphan G-protein–coupled receptors. Orexin neuropeptides (also known as hypocretins) are produced by a small group of neurons in the lateral hypothalamic and perifornical areas, a region classically implicated in the control of mammalian feeding behavior. Orexin neurons project throughout the central nervous system (CNS) to nuclei known to be important in the control of feeding, sleep-wakefulness, neuroendocrine homeostasis, and autonomic regulation. orexin mRNA expression is upregulated by fasting and insulin-induced hypoglycemia. C-fos expression in orexin neurons, an indicator of neuronal activation, is positively correlated with wakefulness and negatively correlated with rapid eye movement (REM) and non-REM sleep states. Intracerebroventricular administration of orexins has been shown to significantly increase food consumption, wakefulness, and locomotor activity in rodent models. Conversely, an orexin receptor antagonist inhibits food consumption. Targeted disruption of the orexin gene in mice produces a syndrome remarkably similar to human and canine narcolepsy, a sleep disorder characterized by excessive daytime sleepiness, cataplexy, and other pathological manifestations of the intrusion of REM sleep-related features into wakefulness. Furthermore, orexin knockout mice are hypophagic compared with weight and age-matched littermates, suggesting a role in modulating energy metabolism. These findings suggest that the orexin neuropeptide system plays a significant role in feeding and sleep-wakefulness regulation, possibly by coordinating the complex behavioral and physiologic responses of these complementary homeostatic functions.

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Annual Review of Neuroscience

Tập 24 Số 1

429-458

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