Decreased brain histamine content in hypocretin/orexin receptor-2 mutated narcoleptic dogs

Seiji Nishino, Nobuhiro Fujiki, Beth Ripley, Eiko Sakurai, Motohisa Kato, Takehiko Watanabe, Emmanuel Mignot, Kazuhiko Yanai

Research output: Contribution to journalArticlepeer-review

111 Citations (Scopus)

Abstract

A growing amount of evidence suggests that a deficiency in hypocretin/orexin neurotransmission is critically involved in animal and human forms of narcolepsy. Since hypocretin-containing neurons innervate and excite histaminergic tuberomammillary neurons, altered histaminergic neurotransmission may also be involved in narcolepsy. We found a significant decrease in histamine content in the cortex and thalamus, two structures important for histamine-mediated cortical arousal, in Hcrtr-2 mutated narcoleptic Dobermans. In contrast, dopamine and norepinephrine contents in these structures were elevated in narcoleptic animals, a finding consistent with our hypothesis of altered catecholaminergic transmission in these animals. Considering the fact that histamine promotes wakefulness, decreases in histaminergic neurotransmission may also account for the sleep abnormalities in hypocretin-deficient narcolepsy.

Original languageEnglish
Pages (from-to)125-128
Number of pages4
JournalNeuroscience Letters
Volume313
Issue number3
DOIs
Publication statusPublished - 2001 Nov 9

Keywords

  • Dopamine
  • Histamine
  • Hypocretin
  • Narcolepsy
  • Norepínephrine
  • Orexin

ASJC Scopus subject areas

  • Neuroscience(all)

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