| Project/Area Number |
20K08089
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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 | Juntendo University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
桝 正幸 筑波大学, 医学医療系, 教授 (20243032)
桝 和子 筑波大学, 医学医療系, 講師 (50344883)
鎌形 康司 順天堂大学, 医学部, 准教授 (60568153)
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| Project Period (FY) |
2020-04-01 – 2023-03-31
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| Project Status |
Completed (Fiscal Year 2022)
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| Budget Amount *help |
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2022: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2021: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2020: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
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| Keywords | endosulfatase / heparan sulfate / MRI / axon guidance / corpus callosum / ヘパラン硫酸等プロテオグリカン / 軸索ガイダンス / ノックアウトマウス / 透明化技術 / 拡散MRI解析 |
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| Outline of Research at the Start |
経回路形成を多段階で分子生物学的に検証することは、正常脳発達の理解を深めるだけでなく、精神神経疾患の病態解明、診断方法開発に重要である。神経回路形成において軸索ガイダンスに関わる分子群を調節する“制御要素”の一つとしてヘパラン硫酸（HS）が知られるが、近年、特異的脱硫酸化によりHS鎖の機能をチューニングする細胞外酵素sulfatase1及び2（Sulf1/2）の存在が注目されている。本研究では神経回路形成障害モデルとしてこれらの二重ノックアウトマウス（Sulf1/2 DKO）を用い、巨視的および顕微鏡的解析を行い比較検討する。
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| Outline of Final Research Achievements |
We mapped neural circuit dysplasia by next-generation diffusion MRI analysis including diffusion tensor and three-dimensional construction of confocal images of transparent brain. By combining the innovative brain clearing technology and cutting-edge MRI technology proposed in recent years, this research has not only elucidated the function of sulfatase in axon guidance, but also a new neuropsychiatric disorder with minute structural abnormalities.
We reported impaired commissural fibers in the brains of Sulf1/2 DKO mice using radiological and histological methods. Using fiber tractography analysis, we found abnormalities in the commissural fiber system of the corpus callosum and dorsal hippocampal commisure and confirmed these histological abnormalities by FluoroMyelin staining and anterograde tracing of the DHC fibers. These results indicate that Sulf1/2 play an important role in the normal development of commissural fibers.
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| Academic Significance and Societal Importance of the Research Achievements |
This study not only elucidated the role of Sulf1/2 in commissure formation but also contributed to the search for new surrogate markers for psychiatric and neurological disorders associated with structural abnormalities.
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