Elucidation of the etiology of neurodevelopmental disorders through multi-scale omics analysis
| Project/Area Number |
20K21479
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| Research Category |
Grant-in-Aid for Challenging Research (Exploratory)
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| Allocation Type | Multi-year Fund |
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| Review Section |
Medium-sized Section 47:Pharmaceutical sciences and related fields
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| Research Institution | Osaka University |
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Principal Investigator |
Kasai Atsushi 大阪大学, 大学院薬学研究科, 准教授 (40454649)
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| Project Period (FY) |
2020-07-30 – 2023-03-31
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| Project Status |
Completed (Fiscal Year 2022)
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| Budget Amount *help |
¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000)
Fiscal Year 2021: ¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000)
Fiscal Year 2020: ¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000)
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| Keywords | 自閉スペクトラム症 / 全脳 / fate mapping / 発達障害 / イメージング / 脳 / 発生 / 細胞移動 / 発生期 / 先制医療 / シングルセル |
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| Outline of Research at the Start |
本課題では、発達障害発症のメカニズムを明らかにし先制医療・新規治療法の確立に貢献する画期的シーズを創出するため、胎生期の神経細胞の全脳レベルの移動・空間配置の定量的な評価法を確立し、発達障害モデル動物の細胞の分化・分布の脳内変化を明らかにする。さらに、最も影響される細胞群から遺伝子発現解析を実施し、脳内変化の新たなメカニズムを提唱する。さらにそのメカニズムに基づいて薬理学的に介入し、因果関係を明らかにする。
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| Outline of Final Research Achievements |
The etiology of neurodevelopmental disorders, such as autism spectrum disorders, remains unclear, and the current interventions are severely limited. In this study, we aimed to elucidate the etiology of developmental disorders by combining birthdate tagging techniques during the cortical development period with whole-brain imaging to identify abnormal cell populations. Our findings revealed that heterogeneity in the distribution of neurons differentiating at E13.5 within the cerebral cortex, attributed to epigenetic changes. Additionally, we observed significant alterations in the distribution of inhibitory neurons compared to excitatory neurons. These findings contribute to future drug discovery research therapeutic target for neurodevelomental disorders.
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| Academic Significance and Societal Importance of the Research Achievements |
発達障害モデルマウスの脳形成期に生じる脳構造異常の詳細は不明であった。本研究により、大脳皮質の構造異常の詳細が明らかになったことから、今後これまで停滞してきた発達障害の発症メカニズムに迫ることが期待される。
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Report
(4 results)
Research Products
(11 results)
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[Presentation] Intranasal oxytocin administration suppresses social contact-induced neural activity in a POGZ-Q1038R mutant mouse model of autism spectrum disorder2022
Author(s)
Kitagawa K, Baba M, Takemoto T, Tanuma M, Hayashida M, Yamaguchi S, Ago Y, Seiriki K, Hayata-Takano A, Takuma K, Kasai A, Hashimoto H, Nakazawa T
Organizer
Neuroscience 2022
Related Report
Int'l Joint Research
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