Inhibitory effects of aripiprazole on interferon-γ-induced microglial activation via intracellular Ca2+ regulation in vitro

Takahiro Kato, Yoshito Mizoguchi, Akira Monji, Hideki Horikawa, Satoshi O. Suzuki, Yoshihiro Seki, Toru Iwaki, Sadayuki Hashioka, Shigenobu Kanba

研究成果: ジャーナルへの寄稿学術誌査読

109 被引用数 (Scopus)

抄録

The activation of the inflammatory/immunological response system is suggested to be related to the pathophysiology of schizophrenia. Aripiprazole is a novel atypical antipsychotic, which is a high-affinity dopamine D2 receptor partial agonist. Atypical antipsychotics, all of which have dopamine D2 receptor antagonism, have recently reported to have significantly inhibitory effects on interferon (IFN)-γ-induced microglial activation in vitro. In the present study, we investigated whether or not aripiprazole also has anti-inflammatory effect on IFN-γ-induced microglial activation. Not quinpirole, dopamine D2 full agonist, but aripiprazole significantly inhibited the generation of nitric oxide (NO) and tumor necrosis factor (TNF)-α from IFN-γ-activated microglia and suppressed the IFN-γ-induced elevation of intracellular Ca2+ concentrations ([Ca2+]i) in murine microglial cells. Increased [Ca2+]i has been reported to be required, but by itself not sufficient, for the release of NO and certain cytokines. As a result, we can speculate that aripiprazole may inhibit IFN-γ-induced microglial activation through the suppression of IFN-γ-induced elevation of [Ca2+]i in microglia. Our results demonstrated that not only antipsychotics which have dopamine D2 receptor antagonism but also aripiprazole have anti-inflammatory effects via the inhibition of microglial activation. Antipsychotics may therefore have a potentially useful therapeutic effect on patients with schizophrenia by reducing the microglial inflammatory reactions.

本文言語英語
ページ(範囲)815-825
ページ数11
ジャーナルJournal of Neurochemistry
106
2
DOI
出版ステータス出版済み - 7月 2008

!!!All Science Journal Classification (ASJC) codes

  • 生化学
  • 細胞および分子神経科学

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