| Project/Area Number |
18K07727
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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 52040:Radiological sciences-related
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| Research Institution | Tohoku Medical and Pharmaceutical University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
桑原 義和 東北医科薬科大学, 医学部, 准教授 (00392225)
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| Project Period (FY) |
2018-04-01 – 2024-03-31
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| Project Status |
Completed (Fiscal Year 2023)
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| Budget Amount *help |
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2021: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
Fiscal Year 2020: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2019: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2018: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
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| Keywords | DNA損傷 / 神経分化 / 未分化 / DNA損傷応答 / 放射線感受性 / 細胞周期 / 分裂細胞 / 神経組織 / 神経細胞 / 分化 / 放射線 / 感受性 |
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| Outline of Final Research Achievements |
Using transgenic mice expressing EGFP-53BP1 fusion fluorescent protein that accumulates at DNA damage sites, we created and analyzed mice to detect DNA damage focus formation, one of a DNA damage response (DDR) in hippocampal neurons. In hippocampal neurons within the tissue, focus formation was suppressed (Off), but when these cells were dissociated and cultured as primary cultures, focus formation resumed (On). This suggests that in highly differentiated neurons within tissue, DDR is suppressed, whereas in primary cultures where the cells revert to a less differentiated state, DDR is reactivated.
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| Academic Significance and Societal Importance of the Research Achievements |
増殖の活発な胎児・子供の組織では未分化な細胞が分裂し、分化した組織では細胞は分裂・増殖を止め停止期にある。未分化で分裂能が高い細胞は放射線感受性が高く、分化した細胞は感受性が低いことが知られているが、その分子メカニズムは明らかではない。
胎児期や幼少期の放射線ダメージは神経系で大きく、精神運動発達遅延を引き起こす。小児の脳腫瘍に放射線治療を行った際に、生存者では海馬の正常発達が損なわる。放射線や酸化ストレスによるDNA損傷を、神経組織の分化、発達段階別に生きたまま評価した研究は少ない。神経組織における未分化性とDNA損傷応答の関係を明らかにし、発達と放射線感受性の関係を明らかする研究である。
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