• Search Research Projects
  • Search Researchers
  • How to Use
  1. Back to previous page

Mapping of abnormal neural circuit formation by diffusion tensor MRI and 3D construction of confocal microscope images

Research Project

Project/Area Number 20K08089
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 52040:Radiological sciences-related
Research InstitutionJuntendo University

Principal Investigator

Kerever Aurelien  順天堂大学, 医学部, 特任助教 (70623594)

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)
Project Period (FY) 2020-04-01 – 2023-03-31
Project Status Completed (Fiscal Year 2022)
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)
Keywordsendosulfatase / 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
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。

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.

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.

Report

(4 results)
  • 2022 Annual Research Report   Final Research Report ( PDF )
  • 2021 Research-status Report
  • 2020 Research-status Report
  • Research Products

    (11 results)

All 2022 2021 2020

All Journal Article (5 results) (of which Int'l Joint Research: 5 results,  Peer Reviewed: 4 results,  Open Access: 2 results) Presentation (6 results)

  • [Journal Article] α-1,6-Fucosyltransferase Is Essential for Myogenesis in Zebrafish2022

    • Author(s)
      Hayashiji Nozomi、Kawahara Genri、Xu Xing、Fukuda Tomohiko、Kerever Aurelien、Gu Jianguo、Hayashi Yukiko K.、Arikawa-Hirasawa Eri
    • Journal Title

      Cells

      Volume: 12 Issue: 1 Pages: 144-144

    • DOI

      10.3390/cells12010144

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Diffusion magnetic resonance tractography-based evaluation of commissural fiber abnormalities in a heparan sulfate endosulfatase-deficient mouse brain2022

    • Author(s)
      Tsuji Yusuke、Kerever Aurelien、Furukawa Toshiki、Kamagata Koji、Saito Yuya、Aoki Shigeki、Hata Junichi、Okano Hideyuki、Kobayashi Kenta、Okada Takuya、Miya Ken、Keino-Masu Kazuko、Masu Masayuki、Arikawa-Hirasawa Eri
    • Journal Title

      Magnetic Resonance Imaging

      Volume: 88 Pages: 123-131

    • DOI

      10.1016/j.mri.2022.01.017

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Optimal Extracellular Matrix Niches for Neurogenesis: Identifying Glycosaminoglycan Chain Composition in the Subventricular Neurogenic Zone2021

    • Author(s)
      Kerever Aurelien、Arikawa-Hirasawa Eri
    • Journal Title

      Frontiers in Neuroanatomy

      Volume: 15 Pages: 4-10

    • DOI

      10.3389/fnana.2021.764458

    • Related Report
      2021 Research-status Report
    • Int'l Joint Research
  • [Journal Article] Regulation of fractone heparan sulfate composition in young and aged subventricular zone neurogenic niches2021

    • Author(s)
      Kerever Aurelien、Nagahara Fumina、Keino-Masu Kazuko、Masu Masayuki、van Kuppevelt Toin H、Viv?s Romain R、Arikawa-Hirasawa Eri
    • Journal Title

      Glycobiology

      Volume: 31 Issue: 11 Pages: 1531-1542

    • DOI

      10.1093/glycob/cwab081

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Increased Risk of Aortic Dissection with Perlecan Deficiency2021

    • Author(s)
      Nonaka Risa、Iesaki Takafumi、Kerever Aurelien、Arikawa-Hirasawa Eri
    • Journal Title

      International Journal of Molecular Sciences

      Volume: 23 Issue: 1 Pages: 315-315

    • DOI

      10.3390/ijms23010315

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Presentation] Sulf1/2 ダブルノックアウトマウスの大脳皮質における血管網構築の3次元解析2022

    • Author(s)
      Kazuteru Murakoshi, Aurelien Kerever, Ryusei Abe, Kazuko Keino-Masu, Masayuki Masu, Eri Arikawa-Hirasawa.
    • Organizer
      第54回日本結合組織学会学術大会
    • Related Report
      2022 Annual Research Report
  • [Presentation] 3D vascular topology analysis reveals impaired microvascular network in the cortex of perlecan KO mice.2022

    • Author(s)
      Aurelien Kerever, Kazuteru Murakoshi, Fumihiro Kokaji, Eri Arikawa-Hirasawa
    • Organizer
      第95回 日本生化学会大会
    • Related Report
      2022 Annual Research Report
  • [Presentation] Sulf1 and sulf2 contribution to fractones heparan sulfate composition in the neurogenic niche.2021

    • Author(s)
      Aurelien Kerever, Kazuko Keino-Masu, Masayuki Masu, Toin van Kuppevelt, Romain R. Vivès, Eri Arikawa-Hirasawa.
    • Organizer
      第53回 日本結合組織学会学術大会 2020年
    • Related Report
      2021 Research-status Report
  • [Presentation] Culture of oligodendrocyte on decellularized tissue for the study of cell/ECM interaction.2021

    • Author(s)
      Hinata Nishimura, Tatsuki Ono, Kazuteru Murakoshi, Ryusei Abe, Aurelien Kerever, Eri Arikawa-Hirasawa.
    • Organizer
      第53回 日本結合組織学会学術大会 2020年
    • Related Report
      2021 Research-status Report
  • [Presentation] Evaluation of corpus callosum abnormalities in heparan sulfate endosulfatase Sulf1/2 deficient brain2021

    • Author(s)
      Furukawa Toshiki, Yusuke Tsuji, Aurelien Kerever, Yuya Saito, Koji Kamagata, Kazuko Keino-Masu, Masayuki Masu, Junichi Hata, Shigeki Aoki, Eri Arikawa-Hirasawa
    • Organizer
      第53回 日本結合組織学会学術大会 2020年
    • Related Report
      2021 Research-status Report
  • [Presentation] Abnormality of corpus callosum in Sulf1/2 brain evaluated by diffusion tensor imaging2020

    • Author(s)
      辻裕介
    • Organizer
      日本神経学会2020
    • Related Report
      2020 Research-status Report

URL: 

Published: 2020-04-28   Modified: 2024-01-30  

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi