Understanding brain and cardiac pathology in schizophrenia using 22q11.2 deletion patient-derived iPS cells.

2020 Fiscal Year Final Research Report

• Project/Area Number: 18K19511
• Research Category: Grant-in-Aid for Challenging Research (Exploratory)
• Allocation Type: Multi-year Fund
• Review Section: Medium-sized Section 52:General internal medicine and related fields
• Research Institution: Nagoya University
• Principal Investigator: Ozaki Norio 名古屋大学, 医学系研究科, 教授 (40281480)
• Project Period (FY): 2018-06-29 – 2021-03-31
• Keywords: 22q11.2欠失 / iPS細胞 / 統合失調症 / 脳病態 / 心臓病態

Outline of Final Research Achievements

We have to solve the two main issues in schizophrenia: (1) the existence of many refractory cases due to unclear brain pathophysiology, (2) the high mortality rate due to complications of cardiac disease and cardiovascular side effects of antipsychotic drugs. To tackle the above-mentioned issues, we aimed to generate cardiomyocytes and neurons from 22q11.2 deletion syndrome patient-derived iPS cells and clarify the pathophysiology of heart and brain. As a result, we revealed the involvement of vulnerability to endoplasmic reticulum stress in dopaminergic neurons as one of the causes in brain pathophysiology. In addition, we established the method of differentiation into cardiomyocytes and electrophysiological analysis of cardiomyocytes. However, due to the discontinuation of the cardiomyocytes differentiation kit, we were forced to suspend our research and were not able to conduct a detailed analysis during this study.

Free Research Field

精神医学分野

Academic Significance and Societal Importance of the Research Achievements

統合失調症の臨床課題の解決には心臓及び脳双方の病態とその関連性についての理解が不可欠である。本研究では22q11.2欠失症候群患者からiPS細胞を樹立し、心筋細胞及び神経細胞を作製した。これらは統合失調症患者の心臓と脳双方の病態を反映するモデルとして有用と考えられ、今後の詳細な解析により病態解明への一歩となることが期待される。さらに、神経細胞を用いた解析では統合失調症患者の脳病態の一つとして小胞体ストレスに対する脆弱性の関与を明らかにしており、病態に基づく治療薬や将来的な発症予防法の開発に繋がることが期待される。