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Narcolepsy pp 11-23 | Cite as

Orexin (Hypocretin) and Narcolepsy

  • Michihiro MiedaEmail author
  • Takeshi Sakurai
Chapter

Abstract

Orexins (hypocretins) are neuropeptides expressed exclusively by neurons in the lateral and perifornical hypothalamus in the brain. Selective degeneration of orexin-producing neurons has been established as the cause of human narcolepsy, a debilitating neurological disease characterized by excessive daytime sleepiness and cataplexy. Orexin neurons are thought to maintain and stabilize wakefulness through their interaction with monoaminergic and cholinergic neurons implicated in the regulation of states of sleep and wakefulness, and they are mediated by two G-protein-coupled receptors that show differential expression patterns depending on brain region and neuron type. Furthermore, the replacement of orexins may prevent narcoleptic symptoms in animal models of narcolepsy. Thus, the discovery of a causal relationship between deficient orexin signaling and narcolepsy has allowed tremendous progress in our understanding of the pathophysiology of narcolepsy, as well as raised the possibility of novel diagnoses and treatments for narcolepsy. Here, we review the current understanding of how the orexinergic system regulates sleep and wakefulness and how its deficiency causes narcolepsy.

Keywords

Orexin Hypocretin Narcolepsy Sleep and wakefulness Monoamine Emotion 

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Copyright information

© Springer International Publishing Switzerland 2016

Authors and Affiliations

  1. 1.Faculty of Medicine, Department of Molecular Neuroscience and Integrative PhysiologyKanazawa UniversityKanazawaJapan

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