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2021 Fiscal Year Final Research Report

Modeling neurodevelopment of frontal cortex and synapse formation using schizophrenia patient-derived iPS cells.

Research Project

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Project/Area Number 18K15516
Research Category

Grant-in-Aid for Early-Career Scientists

Allocation TypeMulti-year Fund
Review Section Basic Section 52030:Psychiatry-related
Research InstitutionKobe University

Principal Investigator

Noriomi Eguchi  神戸大学, 医学部附属病院, 助教 (80814566)

Project Period (FY) 2018-04-01 – 2022-03-31
Keywords統合失調症 / iPS細胞 / 幹細胞 / 大脳皮質 / 中脳 / ドーパミン神経
Outline of Final Research Achievements

The purpose of the study is to analyze neurodevelopment and synaptogenesis of prefrontal cortex which possible cause of occurring schizophrenia. We generated induced pluripotent stem cells (iPSCs) derived from schizophrenia patients and healthy controls and induced neural tissues containing prefrontal cortex-like structures. Morphological analysis of layer structures including neural stem cells and neurons showed no significant difference between schizophrenia and control. Next, we induced dopaminergic neurons and tissues including midbrain dopaminergic neurons to investigate neurodevelopment of midbrain. We successfully obtained neurons and neural tissues, but the efficiency was not enough to analyze morphological alteration of dopaminergic neurons and neural tissues derived from schizophrenia patients. For further investigation, we need to improve the efficiency of our experimental procedures for differentiating iPSCs.

Free Research Field

精神医学

Academic Significance and Societal Importance of the Research Achievements

本研究は統合失調症の病態と考えられているドーパミン仮説に基づき、統合失調症患者のドーパミン神経、および中脳ドーパミン神経と大脳皮質との間のシナプスで起こっている異常を実験的に再現し、生物モデルとして利用可能な実験系を構築することを目的とした。iPS細胞を用い大脳皮質、中脳ドーパミン神経を再現することには成功し、大脳皮質の発生において形態的な異常はないことを見出した。統合失調症の病態解明と更なる治療法の開発のためには、中脳ドーパミン神経の再現と解析が求められる。今後更なる研究が必要である。

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Published: 2023-01-30  

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