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The hypocretin/orexin system in health and disease

Seiji Nishino1

  • 1Center for Narcolepsy, Stanford University, School of Medicine, Psychiatry and Behavioral Sciences, Palo Alto, California 94304, USA.

Biological Psychiatry
|July 23, 2003
PubMed

Insights

Researchers identified hypocretin/orexin genes as key to narcolepsy in animals. Hypocretin deficiency, not gene mutations, is linked to human narcolepsy, suggesting a complex hypothalamic disorder.

Area of Science:

  • Neuroscience
  • Genetics
  • Sleep Medicine

Background:

  • Narcolepsy pathogenesis in animals has been elucidated through genetic studies.
  • Hypocretin/orexin ligand and receptor genes are critical in animal models of narcolepsy.

Purpose of the Study:

  • To identify genes involved in narcolepsy pathogenesis.
  • To investigate the role of hypocretins/orexins in narcolepsy.
  • To understand the complexity of hypocretin-deficient human narcolepsy.

Main Methods:

  • Positional cloning in a canine model of narcolepsy.
  • Gene knockouts in mice.

Main Results:

  • Hypocretin/orexin ligand and receptor genes identified as key to narcolepsy in animals.
  • Mutations in hypocretin-related genes are rare in humans.
  • Hypocretin-ligand deficiency is prevalent in human narcolepsy cases.

Conclusions:

  • Hypocretin-ligand deficiency is a primary cause of human narcolepsy.
  • Human narcolepsy is a complex hypothalamic disorder, not just a sleep disorder.
  • This condition serves as a model for studying hypothalamic function.

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