Study for mechanism of neural tube defect with cell culture system

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K07833
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 51030:Pathophysiologic neuroscience-related
• Research Institution: Fujita Health University
• Principal Investigator: Omi Minoru 藤田医科大学, 医学部, 助教 (00400416)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: 神経発生

Outline of Final Research Achievements

Neural tube defect is a congenital disease and causes serious problems like movement disorder. As its incidence rate is high, 0.1 - 0.2%, therapies for this disease have to be developed as soon as possible.
Valproic acid is a chemical which induces neural tube defect in embryos of human and mouse. To elucidate the mechanism of the neural tube defect, effects of valproic acid on neural cells were studied. When cultured neural cells derived from es cells were treated with valproic acid, cell death was increased. RNA-seq analysis indicated over one thousand genes that were affected by valproic acid. One of the gene was overexpressed, cell death was increase. On the other hand, downregulation of the gene with shRNA show tendency of cell death suppression. These results suggest that valproic acid may cause neural tube defect by inducing cell death and that the picked-up gene may mediate the effect of valproic acid.

Free Research Field

神経科学

Academic Significance and Societal Importance of the Research Achievements

神経管異常は中枢神経の先天的形成異常であり、脊椎二分症や脳ヘルニアといった中枢神経の奇形を引き起こし、運動機能などに支障を来す。重篤な場合では出生直後に死にいたる。神経管異常の発症率は0.1%から0.2%と極めて高く、生涯にわたって健康面に問題を抱え続けることになるため、その発症機構の解明および予防法や治療法の開発は医学的にも社会的にも重要な課題である。本研究では神経管異常を誘発するバルプロ酸を用い解析を行ったところ、バルプロ酸は神経細胞死を誘発している可能性が示唆された。また、その作用を介在する遺伝子が候補として挙げられた。これらの結果は神経管異常の仕組みの解明や予防に資すると考えられる。