Aripiprazole inhibits polyI:C-induced microglial activation possibly via TRPM7

Mina Sato-Kasai, Takahiro A. Kato, Masahiro Ohgidani, Yoshito Mizoguchi, Noriaki Sagata, Shogo Inamine, Hideki Horikawa, Kohei Hayakawa, Norihiro Shimokawa, Sota Kyuragi, Yoshihiro Seki, Akira Monji, Shigenobu Kanba

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Abstract

Viral infections during fetal and adolescent periods, as well as during the course of schizophrenia itself have been linked to the onset and/or relapse of a psychosis. We previously reported that the unique antipsychotic aripiprazole, a partial D2 agonist, inhibits the release of tumor necrosis factor (TNF)-α from interferon-γ-activated rodent microglial cells. Polyinosinic-polycytidylic acid (polyI:C) has recently been used as a standard model of viral infections, and recent in vitro studies have shown that microglia are activated by polyI:C. Aripiprazole has been reported to ameliorate behavioral abnormalities in polyI:C-induced mice. To clarify the anti-inflammatory properties of aripiprazole, we investigated the effects of aripiprazole on polyI:C-induced microglial activation in a cellular model of murine microglial cells and possible surrogate cells for human microglia. PolyI:C treatment of murine microglial cells activated the production of TNF-α and enhanced the p38 mitogen-activated protein kinase (MAPK) pathway, whereas aripiprazole inhibited these responses. In addition, polyI:C treatment of possible surrogate cells for human microglia markedly increased TNF-α mRNA expression in cells from three healthy volunteers. Aripiprazole inhibited this increase in cells from two individuals. PolyI:C consistently increased intracellular Ca2 + concentration ([Ca2 +]i) in murine microglial cells by influx of extracellular Ca2 +. We demonstrated that transient receptor potential in melastatin 7 (TRPM7) channels contributed to this polyI:C-induced increase in [Ca2 +]i. Taken together, these data suggest that aripiprazole may be therapeutic for schizophrenia by reducing microglial inflammatory reactions, and TRPM7 may be a novel therapeutic target for schizophrenia. Further studies are needed to validate these findings.

Original languageEnglish
Pages (from-to)35-43
Number of pages9
JournalSchizophrenia research
Volume178
Issue number1-3
DOIs
Publication statusPublished - Dec 1 2016

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All Science Journal Classification (ASJC) codes

  • Psychiatry and Mental health
  • Biological Psychiatry

Cite this

Sato-Kasai, M., Kato, T. A., Ohgidani, M., Mizoguchi, Y., Sagata, N., Inamine, S., ... Kanba, S. (2016). Aripiprazole inhibits polyI:C-induced microglial activation possibly via TRPM7. Schizophrenia research, 178(1-3), 35-43. https://doi.org/10.1016/j.schres.2016.08.022