Greatly increased numbers of histamine cells in human narcolepsy with cataplexy

Joshi John, Thomas C. Thannickal, Ronald McGregor, Lalini Ramanathan, Hiroshi Ohtsu, Seiji Nishino, Noriaki Sakai, Akhiro Yamanaka, Carly Stone, Marcia Cornford, Jerome M. Siegel

Research output: Contribution to journalArticlepeer-review

66 Citations (Scopus)

Abstract

Objective To determine whether histamine cells are altered in human narcolepsy with cataplexy and in animal models of this disease. Methods Immunohistochemistry for histidine decarboxylase (HDC) and quantitative microscopy were used to detect histamine cells in human narcoleptics, hypocretin (Hcrt) receptor-2 mutant dogs, and 3 mouse narcolepsy models: Hcrt (orexin) knockouts, ataxin-3-orexin, and doxycycline-controlled-diphtheria-toxin-A- orexin. Results We found an average 64% increase in the number of histamine neurons in human narcolepsy with cataplexy, with no overlap between narcoleptics and controls. However, we did not see altered numbers of HDC cells in any of the animal models of narcolepsy. Interpretation Changes in histamine cell numbers are not required for the major symptoms of narcolepsy, because all animal models have these symptoms. The histamine cell changes we saw in humans did not occur in the 4 animal models of Hcrt dysfunction we examined. Therefore, the loss of Hcrt receptor-2, of the Hcrt peptide, or of Hcrt cells is not sufficient to produce these changes. We speculate that the increased histamine cell numbers we see in human narcolepsy may instead be related to the process causing the human disorder. Although research has focused on possible antigens within the Hcrt cells that might trigger their autoimmune destruction, the present findings suggest that the triggering events of human narcolepsy may involve a proliferation of histamine-containing cells. We discuss this and other explanations of the difference between human narcoleptics and animal models of narcolepsy, including therapeutic drug use and species differences. Ann Neurol 2013;74:786-793

Original languageEnglish
Pages (from-to)786-793
Number of pages8
JournalAnnals of Neurology
Volume74
Issue number6
DOIs
Publication statusPublished - 2013 Dec

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology

Fingerprint Dive into the research topics of 'Greatly increased numbers of histamine cells in human narcolepsy with cataplexy'. Together they form a unique fingerprint.

Cite this