The neurochemistry of awakening: findings from sleep disorder narcolepsy.
Recent progress in our understanding of the pathophysiology of excessive sleepiness (EDS) is particularly indebted to the 1999 discovery of narcolepsy genes (i.e., hypocretin receptor and peptide genes) in animals and the subsequent discovery of hypocretin ligand deficiency in idiopathic cases of human narcolepsy-cataplexy. Hypocretin deficiency is also involved in many cases of symptomatic narcolepsy and EDS. Changes in other neurotransmitter systems (such as monoamines and acetylcholine) previously reported in these conditions are likely to be secondary to the impaired hypocretin neurotransmission; however, these may also mediate the sleep abnormalities seen in hypocretin deficient narcolepsy. The pathophysiology of hypocretin non-deficient narcolepsy is debated. Similarly, the pathophysiology of idiopathic hypersomnia, another defined primary hypersomnia, is largely unknown. This chapter discusses our current understanding of the neurochemistry of EDS, a disease of awakening.
Sleep and Circadian Neurobiology Laboratory, Stanford University School of Medicine, Stanford, CA 94304-5489, USA.
Seiji
S
Nishino
Yohei
Y
Sagawa
D000818:Animals; D001923:Brain Chemistry / Q000502:physiology*; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000172:deficiency; D009290:Narcolepsy / Q000378:metabolism* / Q000503:physiopathology*; D009479:Neuropeptides / Q000172:deficiency; D000068797:Orexins; D012893:Sleep Wake Disorders / Q000378:metabolism / Q000503:physiopathology; D014851:Wakefulness / Q000502:physiology*
D047908:Intracellular Signaling Peptides and Proteins; D009479:Neuropeptides; D000068797:Orexins