The Experimental Studies Of Orexin And Sleep

In 1998, two independent group discovered the hypocretin-1 and -2 (also referred to as orexin-A and -B). Several findings from past year have suggested that orexin might play a role in sleep regulation: first, a mutation of the orexin recaptor-2 gene has been found in narcoleptic dogs. In addition, orexin knockout mice (lacking orexin peptides) exhibit a phenotype that is strikingly similar to human narcolepsy patients. Orexins are synthesized by neurons whose somas are restricted to the lateral hypothalamus.The expression of prepro-orexin mRNA was exzamined by RT-PCR in the hypothalamus and cerebral cortex of rat during the sleep-waking cycle and after 4, 8, 12 and 24 hours sleep deprivation. During the sleep-waking cycle, the expression of prepro-orexin mRNA in hypothalamus is higher than that in cerebral cortex, and there was a diurnal fluctuation. After 4 hours of sleep deprivation, there was no change of the expression of prepro-orexin mRNA in hypothalamus and cerebral cortex. As the prolong of time in sleep deprivation, the expression of prepro-orexin mRNA elevated gradually inhypothalamus and cerebral cortex.In addition, hypothalamic neurons that contain hypocreti(orexin) express c-fos were observed by immunohistochemical technique duringactive wakefulness and 48h total sleep deprivation. The majority of hypocretinergic neuron expressed c-fos during darkness. Only a small number of these cells expressed c-fos during lightness. The maximum of these cells expressed c-fos during 48h total sleep deprivation. The results shows hyporexinergic neurons in hypthalamus facilitate the wakefulness. In order to maintenance wakefulness, more hypocretinergic neuron activated. This is one of mechanisms of orexin in sleep regulation.It is concluded the hypothalamus is a central of the regulation of sleep and wakefulness. Orexin neurotransmitter system controls the sleep-waking clcle. There was no diurnal fluctuation of orexin in cerebral cortex. The role of orexin is maintenance of wakefulness. Therefore, the secretion of orexin increased to maintain wakefulness.