Circuit mechanisms of sleepiness and cataplexy in narcolepsy.
Narcolepsy is a debilitating sleep disorder caused by loss of orexin neurons in the lateral hypothalamus. Excessive daytime sleepiness and cataplexy are the major complaints in narcolepsy, and are associated with impaired quality of life. Although it is unclear how orexin loss causes sleepiness and cataplexy, animal models have been instrumental in identifying the neurobiological underpinnings of narcolepsy because they reliably recapitulate disease symptoms. Current evidence indicates that orexin cell loss causes sleepiness and cataplexy by destabilizing the ability of the circuits that initiate and sustain normal levels of arousal and motor activity. This review highlights the latest research concerning the normal function of the orexin system and how its dysfunction causes narcolepsy symptoms.
Centre for Biological Timing and Cognition, Department of Cell and Systems Biology, University of Toronto, Toronto, ON M5S 3G5, Canada.
Sara
S
Pintwala
Centre for Biological Timing and Cognition, Department of Cell and Systems Biology, University of Toronto, Toronto, ON M5S 3G5, Canada; Centre for Biological Timing and Cognition, Department of Physiology, University of Toronto, Toronto, ON M5S 3G5, Canada. Electronic address: John.peever@utoronto.ca.
John
J
Peever
D000818:Animals; D002385:Cataplexy / Q000503:physiopathology*; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D009290:Narcolepsy / Q000503:physiopathology*; D000068797:Orexins / Q000378:metabolism; D012106:Research / Q000639:trends; D012890:Sleep / Q000502:physiology*
D047908:Intracellular Signaling Peptides and Proteins; D000068797:Orexins