Jerome M. Siegel, sleep disorders, narcolepsy, hypocretin, orexin
Sleep is important and required for the survival and normal homeostasis of vertebrates. Disturbances in the sleep-wake cycle can lead to many sleep disorders, one of which is narcolepsy. Narcolepsy is a disabling sleep disorder characterized by excessive daytime sleep, cataplexy (sudden loss of muscle tone in response to strong emotion or laughter), hallucinations, and sleep paralysis. To date, the pathological and biological basis of narcolepsy is poorly understood. My lab first discovered, in canines and humans, dysfunctional neurons that affect the sleep-wake cycle in narcolepsy, as well as neurodegeneration of brainstem and hypothalamic neurons. Other labs have identified mutations in hypocretin (orexin) receptor genes in canine narcoleptics. An orexin knockout mice model mimics the narcoleptic phenotype seen in humans and dogs. More recently, a hypocretin gene mutation has been identified in at least one human narcoleptic. Given that orexin is critical for the regulation of feeding behavior, opens the door to investigate energy homeostasis in narcolepsy, as well as in finding a treatment.
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