2018 Fiscal Year Final Research Report
Modeling of psychiatric disorders using iPSC technologies
| Project/Area Number |
15H04645
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Biological pharmacy
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| Research Institution | Osaka University |
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Principal Investigator |
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| Research Collaborator |
Hashimoto Hitoshi
Hashimoto Ryota
Kuriu Toshihiko
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| Project Period (FY) |
2015-04-01 – 2018-03-31
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| Keywords | iPS細胞 / 統合失調症 / 患者神経細胞 / 分子病態 / 神経細胞分化 / RNA発現解析 / スプライシング反応 / 電気生理学解析 |
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| Outline of Final Research Achievements |
Schizophrenia is a common psychiatric disorder that occurs mainly in adolescence, characterized by positive and negative symptoms. Despite a large number of studies, much remains unknown about the molecular etiology of schizophrenia. In this study, we applied iPSC technologies to generate patients' live neuronal cells that enable us to precisely analyze the disease-associated neuronal phenotype. We analyzed the neural function of iPSC-neurons derived from patients from a family with multiple occurrence of schizophrenia and other patients. In these neurons, we found that the impaired gene expression, splicing events and synaptic functions, all of which may be associated with schizophrenia. These results imply that iPSC-derived neurons of patients with schizophrenia provide important insights into the development of new treatment strategies and biomarkers for diagnosis and treatment efficacy.
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| Free Research Field |
分子神経科学
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| Academic Significance and Societal Importance of the Research Achievements |
統合失調症の病因や病態は不明な点が多く、治療薬の効果も不十分な現状にある。本研究では、直接的に患者由来の神経細胞が解析可能となる患者iPS細胞を介して神経細胞を作製するという、これまでに報告例が少ない新規の系を利用した研究を実施した。その結果、統合失調症と関連することが期待される神経機能の異常（遺伝子発現異常、スプライシング機能異常、及びシナプス機能異常）を同定した。本研究により得られた成果は、疾患の分子病態の同定のみならず、創薬研究、統合失調症の診断や治療に伴う有効性を評価するバイオマーカーの開発、および疾患の細分類系の確立のために極めて有効な基礎データを提供するものである。
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