Narcolepsy and the hypocretin system--where motion meets emotion.

TitleNarcolepsy and the hypocretin system--where motion meets emotion.
Publication TypeJournal Article
Year of Publication2006
AuthorsSiegel JM, Boehmer LN
JournalNature Clinical Practice Neurology [Nature Reviews Neurology]
Date Published2006 Oct
KeywordsAnimals, Brain, Clinical Trials as Topic, Emotions, Humans, Movement, Narcolepsy, Neurons, Neuropeptides

Narcolepsy is a neurological disorder that is characterized by excessive daytime sleepiness and cataplexy--a loss of muscle tone generally triggered by certain strong emotions with sudden onset. The underlying cause of most cases of human narcolepsy is a loss of neurons that produce hypocretin (Hcrt, also known as orexin). These cells normally serve to drive and synchronize the activity of monoaminergic and cholinergic cells. Sleepiness results from the reduced activity of monoaminergic, cholinergic and other cells that are normally activated by Hcrt neurons, as well as from the loss of Hcrt itself. Cataplexy is caused by an episodic loss of activity in noradrenergic cells that support muscle tone, and a linked activation of a medial medullary cell population that suppresses muscle tone. Current treatments for narcolepsy include stimulants to combat sleepiness and antidepressants to reduce cataplexy. Sodium oxybate produces both reductions in cataplexy and improved waking alertness. Future treatments are likely to include Hcrt or Hcrt agonists to reverse the underlying neurochemical deficit.

Alternate JournalNat Clin Pract Neurol
PubMed ID16990828
Grant ListMH64109 / MH / NIMH NIH HHS / United States
NS14610 / NS / NINDS NIH HHS / United States