Hypocretin/orexin, sleep and narcolepsy

The discovery that hypocretins are involved in narcolepsy, a disorder assoc iated with excessive daytime sleepiness, cataplexy and unusually rapid tran sitions to rapid-eye-movement sleep, opens a new field of investigation in the area of sleep control physiology, Hypocretin-1 and -2 (also called orex in-A and -B) are newly discovered neuropeptides processed from a common pre cursor, preprohypocretin, Hypocretin-containing cells are located exclusive ly in the lateral hypothalamus, with widespread projections to the entire n euroaxis. Two known receptors, Hcrtr1 and Hcrtr2, have been reported. The f unctional significance of the hypocretin system is rapidly emerging in both animals and humans. Hypocretin abnormalities cause narcolepsy in dogs, hum an and mice. The role of the hypocretin system in normal sleep regulation i s more uncertain. We believe hypocretin cells drive cholinergic and monoami nergic activity across the sleep cycle. Input from the suprachiasmatic nucl eus to hypocretin-containing neurons may explain the occurrence of clock-de pendent alertness. Other functions are suggested by pharmacological and neu rochemical experiments. These include regulation of food intake, neuroendoc rine function, autonomic nervous system activity and energy balance. (C) 20 01 John Wiley & Sons, Inc.