Histamine regulation of microglia: Gene-environment interaction in the regulation of central nervous system inflammation

Luciana Frick, Maximiliano Rapanelli, Eeman Abbasi, Hiroshi Ohtsu, Christopher Pittenger

Research output: Contribution to journalArticlepeer-review

46 Citations (Scopus)


Microglia mediate neuroinflammation and regulate brain development and homeostasis. Microglial abnormalities are implicated in a range of neuropsychiatric pathology, including Tourette syndrome (TS) and autism. Histamine (HA) is both a neurotransmitter and an immune modulator. HA deficiency has been implicated as a rare cause of TS and may contribute to other neuropsychiatric conditions. In vitro studies suggest that HA can regulate microglia, but this has never been explored in vivo. We used immunohistochemistry to examine the effects of HA deficiency in histidine decarboxylase (Hdc) knockout mice and of HA receptor stimulation in wild-type animals. We find HA to regulate microglia in vivo, via the H4 receptor. Chronic HA deficiency in Hdc knockout mice reduces ramifications of microglia in the striatum and (at trend level) in the hypothalamus, but not elsewhere in the brain. Depletion of histaminergic neurons in the hypothalamus has a similar effect. Microglia expressing IGF-1 are particularly reduced, However, the microglial response to challenge with lipopolysacchariade (LPS) is potentiated in Hdc knockout mice. Genetic abnormalities in histaminergic signaling may produce a vulnerability to inflammatory challenge, setting the state for pathogenically dysregulated neuroimmune responses.

Original languageEnglish
Pages (from-to)326-337
Number of pages12
JournalBrain, Behavior, and Immunity
Publication statusPublished - 2016 Oct 1


  • Basal ganglia
  • H4R receptor
  • IGF-1
  • Lipopolysaccharide

ASJC Scopus subject areas

  • Immunology
  • Endocrine and Autonomic Systems
  • Behavioral Neuroscience


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