Elucidation of molecular mechanisms causing cognitive dysfunction in schizophrenia and development of novel therapeutic strategies

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K15741
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 52030:Psychiatry-related
• Research Institution: University of Tsukuba
• Principal Investigator: Fukuda Mayu 筑波大学, プレシジョン・メディスン開発研究センター, 研究員 (60894798)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: 統合失調症 / 22q11.2欠失症候群 / 認知機能障害

Outline of Final Research Achievements

In this study, in addition to Df(16)A+/- and Setd1a+/-, which have a clear causal relationship with schizophrenia, we conducted various behavioral experiments using Kmt2c+/- and Kmt2e+/-, which are mouse models of a single-gene disorder of neurodevelopmental disorders related to KMT isoforms, and also aimed to perform multi-omics analyses including transcriptomic, metabolomic, and proteomic analyses at different developmental stages using samples obtained from the prefrontal cortex of the mouse brain. The results showed that characteristic behavioral abnormalities were observed in each mouse line, and that several different genes were up- and down-regulated in each mouse line and at each developmental stage.

Free Research Field

神経科学

Academic Significance and Societal Importance of the Research Achievements

統合失調症における認知機能障害はこの疾患の本質であり、長期の治療によっても耐性を示し、患者の社会生活及び社会復帰を拒む。認知機能障害の核となる作業記憶の障害は、推論や認識、意思決定等に深刻な影響を与え、日常生活に重大な支障を来たすため、患者本人、家族、地域社会における経済的、社会的負担も大きい。認知機能障害に対する薬剤の開発は、統一病態生理の不在と複雑な遺伝学的構造により依然として困難であり、革新的な治療法の創出が求められている。本研究の成果が、新規治療法・治療薬の開発の基礎となり、将来的に患者本人、および家族の負担軽減に繋がることが期待される