Molecular pathology of schizophrenia and novel mechanisms of antipsychotics from the perspective of MIF

2020 Fiscal Year Final Research Report

• Project/Area Number: 18K15483
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 52030:Psychiatry-related
• Research Institution: Kobe University
• Principal Investigator: Okazaki Satoshi 神戸大学, 医学部附属病院, 助教 (70722867)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Keywords: 統合失調症 / MIF / アストロサイト / クロザピン / ヒストンアセチル化 / ES細胞 / iPS細胞

Outline of Final Research Achievements

In order to elucidate the pathological mechanism of schizophrenia, we focused on macrophage migration inhibitory factor (MIF). We performed analysis using mouse-derived astrocytes. We observed increased MIF mRNA expression and protein production due to antipsychotics. We further investigated the details of the MIF expression mechanism using clozapine. We found that histone acetylation was involved in the mechanism. These findings suggest that MIF is involved in the pathophysiology of schizophrenia and the unknown action mechanism of antipsychotics. We are going to continue the investigation of the mechanism of MIF in schizophrenia using primary mouse ES cells and human iPS cells derived from patients with schizophrenia.

Free Research Field

精神医学分野

Academic Significance and Societal Importance of the Research Achievements

統合失調症は世界的に有病率約1%の主要な精神疾患であるが、生物学的基盤の詳細は現在も明らかでなく、診断・治療は未だ症状・経過に依存している。本研究により、統合失調症の分子病態および抗精神病薬の未知の作用機序におけるMIFの役割の一端が明らかになった。MIFに着目した統合失調症の研究は世界に先駆けており、学術的意義は高いと考える。また統合失調症の診断や治療応用に繋がる研究成果であり、社会的意義美も高いと考える。