Hypocretins, peptides associated with narcolepsy

Narcolepsy is a chronic disease characterized by excessive somnolence, abrupt transitions from wakefulness to rapid eye movement sleep stage and cataplexy. Experimental evidence show that narcolepsy in humans is a neurodegenerative disease associated with the lost of hypocretin (HCRT) neurons in the lateral hypothalamus. Narcoleptic patients also display a significant diminution in HCRT contents of cerebrospinal fluid. In order to study narcolepsy, several experimental models have been developed. Murine and canine models currently allow us to study this disease. Our laboratory has developed a new experimental rat model of narcolepsy. This model allows us to study the disease from a histological and neurochemical perspective. Elsewhere we have reported that the use of the toxin hypocretin2/saporine (HCRT2/ SAP) selectively destroys hypocretinergic neurons. The loss of these neurons induces a similar behavioural profile as the one observed in other experimental models of narcolepsy. In the present review we describe an overview on narcolepsy, the hypocretinergic system, experimental models in narcolepsy and the use of transplants as an alternative therapeutic tool.