Inhibitory effects of SSRIs on IFN-γ induced microglial activation through the regulation of intracellular calcium

Hideki Horikawa, Takahiro A. Kato, Yoshito Mizoguchi, Akira Monji, Yoshihiro Seki, Takatoshi Ohkuri, Leo Gotoh, Megumi Yonaha, Tadashi Ueda, Sadayuki Hashioka, Shigenobu Kanba

Research output: Contribution to journalArticle

88 Citations (Scopus)

Abstract

Microglia, which are a major glial component of the central nervous system (CNS), have recently been suggested to mediate neuroinflammation through the release of pro-inflammatory cytokines and nitric oxide (NO). Microglia are also known to play a critical role as resident immunocompetent and phagocytic cells in the CNS. Immunological dysfunction has recently been demonstrated to be associated with the pathophysiology of depression. However, to date there have only been a few studies on the relationship between microglia and depression. We therefore investigated if antidepressants can inhibit microglial activation in vitro. Our results showed that the selective serotonin reuptake inhibitors (SSRIs) paroxetine and sertraline significantly inhibited the generation of NO and tumor necrosis factor (TNF)-α from interferon (IFN)-γ-activated 6-3 microglia. We further investigated the intracellular signaling mechanism underlying NO and TNF-α release from IFN-γ-activated 6-3 microglia. Our results suggest that paroxetine and sertraline may inhibit microglial activation through inhibition of IFN-γ-induced elevation of intracellular Ca2+. Our results suggest that the inhibitory effect of paroxetine and sertraline on microglial activation may not be a prerequisite for antidepressant function, but an additional beneficial effect.

Original languageEnglish
Pages (from-to)1306-1316
Number of pages11
JournalProgress in Neuro-Psychopharmacology and Biological Psychiatry
Volume34
Issue number7
DOIs
Publication statusPublished - Oct 1 2010

All Science Journal Classification (ASJC) codes

  • Pharmacology
  • Biological Psychiatry

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