Elucidation of the molecular mechanism of the decline in nerve system function by the glycation stress

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K07555
• 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: Shizuoka Graduate University of Public Health (2023); Tokyo Metropolitan Institute of Medical Science (2021-2022)
• Principal Investigator: Yasue Horiuchi 静岡社会健康医学大学院大学, 社会健康医学研究科, 教授 (00548985)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: 統合失調症 / グリア細胞 / iPS細胞 / アストロサイト / 酸化ストレス / カルボニルストレス

Outline of Final Research Achievements

It is well-known that various types of stress are involved in the onset and changes in symptoms of schizophrenia. "Stress vulnerability," which acts as a nexus between genetic and environmental factors, is considered crucial in both understanding the pathophysiology and developing treatments for the disease. In this study, we found an increase in oxidative and glycation stress in astrocytes derived from patients with schizophrenia. Additionally, we observed the accumulation of Advanced Glycation End Products (AGEs) in these patient-derived astrocytes, suggesting functional abnormalities in astrocytes. Furthermore, it became clear that stress vulnerability varies between different cell types, such as neurons and astrocytes.

Free Research Field

遺伝医学、幹細胞学、遺伝カウンセリング学

Academic Significance and Societal Importance of the Research Achievements

統合失調症のような有病率が高い多因子遺伝疾患iPS細胞由来神経細胞とグリア細胞における解析は国内外でも例がなく作成したiPS細胞リソースの有用性は統合失調症研究において極めて高い。これまでにいくつかの統合失調症患者由来iPS細胞を用いた解析が報告されているが、いずれも患者由来細胞からiPS細胞樹立とニューロンの解析のみにとどまっており臨床症状とつながる解析までには至っていない。本研究で用いる生体試料は臨床情報も備えているため、患者由来細胞の現象を明らかにするだけでなく、その変化が臨床症状とどのように関連するのかという踏み込んだ解析が可能となった。