Anti-inflammatory properties of antipsychotics via microglia modulations: Are antipsychotics a 'fire extinguisher' in the brain of schizophrenia?

T. A. Kato, A. Monji, Y. Mizoguchi, S. Hashioka, H. Horikawa, Y. Seki, M. Kasai, H. Kasai, H. Utsumi, S. Kanba

研究成果: ジャーナルへの寄稿学術誌査読

112 被引用数 (Scopus)

抄録

Schizophrenia is one of the most severe psychiatric diseases noted for its chronic and often debilitating processes; affecting approximately 1% of the world's population, while its etiology and therapeutic strategies still remain elusive. In the 1950s, the discovery of antipsychotic effects of haloperidol and chlorpromazine shifted the paradigm of schizophrenia. These drugs proved to be antagonists of dopamine D2 receptor (D2R), thus dopamine system dysfunction came to be hypothesized in the pathophysiology of schizophrenia, and D2R antagonism against dopamine neurons has been considered as the primary therapeutic target for schizophrenia. In addition, abnormalities of glutamatergic neurons have been indicated in the pathophysiology of schizophrenia. On the other hand, recent neuroimaging studies have shown that not only dementia but also schizophrenic patients have a significant volume reduction of some specific regions in the brain, which indicates that schizophrenia may involve some neurodegenerative process. Microglia, major sources of various inflammatory cytokines and free radicals such as superoxide and nitric oxide (NO) in the CNS, play a crucial role in a variety of neurodegenerative diseases such as dementia. Recent postmortem and positron emission computed tomography (PET) studies have indicated that activated microglia may be present in schizophrenic patients. Recent in vitro studies have suggested the anti-inflammatory effects of antipsychotics on microglial activation. In this article, we review the anti-inflammatory effects of antipsychotics on microglia, and propose a novel therapeutic hypothesis of schizophrenia from the perspective of microglial modulation.

本文言語英語
ページ(範囲)565-574
ページ数10
ジャーナルMini-Reviews in Medicinal Chemistry
11
7
DOI
出版ステータス出版済み - 2011

!!!All Science Journal Classification (ASJC) codes

  • 分子医療
  • 薬理学
  • 創薬
  • 癌研究

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