Role of orexins hypocretins

Sakurai T. (2005). Roles of orexin/hypocretin in regulation of sleep/wakefulness and energy homeostasis. Sleep Med. Rev. 9, 231-41. 

Other activators of the histaminergic system may also be involved in wakefulness. The orexin (i.e. hypocretin) A and B neuropeptides were isolated from rat hypothalamic extracts. A mutation in the orexin-2 receptor gene was found to be associated with canine narcolepsy, and mice lacking the orexin peptide display increases in REM and NREM sleep and a decrease in wakefulness time during the active period of normal rodents. However, the exact role of orexin in physiological sleep and the mechanisms involved have not yet been elucidated. 

Taheri S, Zeitzer JM, Mignot E. The role of hypocretins (orexins) in sleep regulation and narcolepsy. Annu Rev Neurosci 2002 25 283-313. 

The hypocretin/orexin neurotransmitter system may play a central role in narcolepsy. An autoimmune process may cause destruction of hypocretin-producing cells. 

Orexins A and B are an important pair of neurotransmitters (otherwise known as hypocretins 1 and 2), derived from a common precursor. They have a major role in arousal and foodseeking behaviour. Damage to the orexin signalling system leads to narcolepsy (a disorder that causes excessive sleepiness during the day and frequent and uncontrollable episodes of falling asleep). 

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