オレキシンによる摂食、ストレス、睡眠の調節

概要

論文の詳細を見る
Orexin-A and -B are hypothalamic peptides isolated recently from the hypothalamus, and have been shown to stimulate food intake. Orexin neurons in the lateral hypothalamic area (LHA) were shown to receive terminal appositions from neuropeptide Y (NPY) fibers. Orexin neurons are regulated by plasma glucose, leptin and ghrelin levels. These observations suggest that orexin neurons sense the animal's nutritional state. Orexin neurons project widely in the brain, and the physiological role of orexins is likely to be complex. Recent studies suggest that stress activates the orexin-containing neurons in the hypothalamus, releases orexin in the central nervous system and activates corticotropin-releasing hormone (CRH) pathways in the activation of hypothalamo-pituitary-adrenal (HPA) axis. In addition, orexins have been reported to have roles in regulating the sleep-wake cycle. In a canine model, narcolepsy is caused by orexin receptor-2 mutations. Preproorexin knockout mice have narcolepcy. Human narcolepcy is generally not due to gene mutations, but orexin neurotransmission is impaired. Orexin-A in cerebrospinal fluid is undetectable in almost all patients with narcolepsy. This review summarizes roles of orexin in the regulatory mechanism of feeding, stress and sleep.