Histamine from brain resident MAST cells promotes wakefulness and modulates behavioral states

PLoS One. 2013 Oct 18;8(10):e78434. doi: 10.1371/journal.pone.0078434. eCollection 2013.


Mast cell activation and degranulation can result in the release of various chemical mediators, such as histamine and cytokines, which significantly affect sleep. Mast cells also exist in the central nervous system (CNS). Since up to 50% of histamine contents in the brain are from brain mast cells, mediators from brain mast cells may significantly influence sleep and other behaviors. In this study, we examined potential involvement of brain mast cells in sleep/wake regulations, focusing especially on the histaminergic system, using mast cell deficient (W/W(v)) mice. No significant difference was found in the basal amount of sleep/wake between W/W(v) mice and their wild-type littermates (WT), although W/W(v) mice showed increased EEG delta power and attenuated rebound response after sleep deprivation. Intracerebroventricular injection of compound 48/80, a histamine releaser from mast cells, significantly increased histamine levels in the ventricular region and enhanced wakefulness in WT mice, while it had no effect in W/W(v) mice. Injection of H1 antagonists (triprolidine and mepyramine) significantly increased the amounts of slow-wave sleep in WT mice, but not in W/W(v) mice. Most strikingly, the food-seeking behavior observed in WT mice during food deprivation was completely abolished in W/W(v) mice. W/W(v) mice also exhibited higher anxiety and depression levels compared to WT mice. Our findings suggest that histamine released from brain mast cells is wake-promoting, and emphasizes the physiological and pharmacological importance of brain mast cells in the regulation of sleep and fundamental neurobehavior.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Behavior, Animal / physiology*
  • Brain / metabolism*
  • Brain / physiology*
  • Electroencephalography / methods
  • Histamine / metabolism*
  • Histamine Release / physiology*
  • Male
  • Mast Cells / metabolism
  • Mast Cells / physiology*
  • Mice
  • Sleep / physiology
  • Sleep Deprivation / metabolism
  • Sleep Deprivation / physiopathology
  • Wakefulness / physiology*


  • Histamine

Grant support

S.C. is supported by the Excellent Young Researcher Overseas Visit Program (21-8162) of the Japan Society for the Promotion of Science. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.