2023 Fiscal Year Final Research Report
Clarification of the molecular pathogenesis of autism spectrum disorders through the analysis regarding sex differences
| Project/Area Number |
21K06594
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Review Section |
Basic Section 47040:Pharmacology-related
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| Research Institution | Osaka University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
松崎 伸介 森ノ宮医療大学, 保健医療学部, 教授 (60403193)
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| Project Period (FY) |
2021-04-01 – 2024-03-31
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| Keywords | 自閉スペクトラム症 / バルプロ酸 / 性差 / マウス / 社会性障害 |
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| Outline of Final Research Achievements |
The aim of this study was to elucidate the inducing or suppressing molecules involved in the expression of core symptom-like behaviors of autism spectrum disorder (ASD) using the indicators "sex differences" between male and female mice prenatally exposed to VPA, in which the research group of principal investigator established the male VPA-exposed mice as an ASD model. At first, we confirmed that prenatal VPA exposure caused a decrease in social behavior only in male offspring. We further prepared total RNA from the cerebral cortex of male and female mouse embryos at 6 hours after VPA exposure, performed a comprehensive analysis of gene expression using RNA sequencing method, and then detected several dozen molecules that showed significant increases and decreases. Furthermore, we will pick up and identify molecules related to ASD onset from the molecules detected by RNA sequence analysis.
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| Free Research Field |
神経薬理学
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| Academic Significance and Societal Importance of the Research Achievements |
近年の疫学調査より，ASD発症が遺伝的要因だけでは説明できないことが明らかとされ，特に，胎児期の母体の感染や薬物摂取，および産科的合併症など胎生期・周産期の母体環境要因が注目されている．さらにこの4~5年は，遺伝的要因および環境要因とともに“性差”に関する報告が急増しており，“性差”の観点からASDの病態解明にアプローチしようとする研究の潮流が起きている．したがって，“性差”を指標としてASDの病態分子基盤にアプローチを試みた本研究は国内外の動向と一致するものであり，その成果は，ASDの病態研究の発展と新たな治療薬の開発に貢献しうる学術的ならびに社会的意義の高いものと評価される．
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