Molecular mechanisms linking hypoxia exposure and schizophrenia with a focus on MIF.

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K07520
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• 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)
• Co-Investigator(Kenkyū-buntansha): 江口 典臣 神戸大学, 医学部附属病院, 助教 (80814566) ; 蓬莱 政 神戸大学, 医学部附属病院, 講師 (90817826)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: 統合失調症 / MIF / HIF / 低酸素 / SNP / アストロサイト / 神経幹細胞 / iPS細胞

Outline of Final Research Achievements

To elucidate the pathomechanism of schizophrenia, we focused our analysis on macrophage migration inhibitory factor (MIF). Hypoxia exposure, a risk factor for schizophrenia, induces MIF expression via binding of hypoxia-inducible factor (HIF) to the hypoxia response element (HRE) of the MIF promoter SNPrs17004038 on the HRE of the MIF promoter was studied in patient-control association studies and found a significant association . Using mouse astrocytes, hypoxia induced MIF mRNA/protein expression, increased HIF binding to the MIF promoter, and MIF promoter activity was suppressed by mutations or deletions in the HRE. Further studies will continue with mouse neural stem cells and patient iPS cells.

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、統合失調症の低酸素暴露が係る分子病態における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。