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Development of cerebral infarction regeneration method that combines neurogenesis and angiogenesis with new guidance factors

Research Project

Project/Area Number 17K08512
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field General anatomy (including histology/embryology)
Research InstitutionHamamatsu University School of Medicine

Principal Investigator

Yamagishi Satoru  浜松医科大学, 医学部, 准教授 (40372362)

Project Period (FY) 2017-04-01 – 2021-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2019: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
KeywordsNetrin-5 / 神経新生 / 吻側移動流 / DCX / ガイダンス分子 / EdU / 新生神経 / 新生神経細胞 / 軸索ガイダンス因子 / 細胞機能形態学
Outline of Final Research Achievements

The axon guidance molecule Netrin-5, which we reported in 2015, is strongly expressed in neurogenesis related areas, but its function was unknown. In this research project, we focused on the function of Netrin-5 in cerebral infarction, but did not obtain the expected results. However, analysis of Netrin-5 knockout mice revealed abnormal neurogenesis. The cell division cycle in the SVZ was longer and the number of dividing cells was decreased in Netrin-5 knockout mice. In addition, the formation of RMS was disorganized (Ikegaya et al., Front Neuroscience, 2020).
These results indicate that loss of function of Netrin-5 may reflect aging of the brain. In addition, we found that cerebral infarction caused strong upregulation of Netrin-5 in neuroblast and vascular endothelial cells. Therefore, it is expected that new methods such as the establishment of a neurotrophic factor release using the Netrin-5 promoter will be applied to the regeneration of cerebral infarction.

Academic Significance and Societal Importance of the Research Achievements

Netrin-5ノックアウトマウスでニューロブラストの細胞分裂周期の延長と分裂細胞数の減少が見られたため、脳の老化を反映している可能性が考えられる。すなわちNetrin-5投与による脳老化の抑制効果が期待される。また、脳梗塞時にはニューロブラストおよび血管内皮細胞でNetrin-5の強い発現亢進が見られた。したがって、Netrin-5プロモーターを用いた神経栄養因子の放出方法の樹立など、今後視点を変えた新規手法により脳梗塞再生に向けての発展応用が期待される。

Report

(5 results)
  • 2020 Annual Research Report   Final Research Report ( PDF )
  • 2019 Research-status Report
  • 2018 Research-status Report
  • 2017 Research-status Report
  • Research Products

    (18 results)

All 2021 2020 2019 2018 2017

All Journal Article (6 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 6 results,  Open Access: 6 results) Presentation (12 results) (of which Int'l Joint Research: 6 results)

  • [Journal Article] Involvement of Netrins and Their Receptors in Neuronal Migration in the Cerebral Cortex2021

    • Author(s)
      Yamagishi Satoru、Bando Yuki、Sato Kohji
    • Journal Title

      Frontiers in Cell and Developmental Biology

      Volume: 8 Pages: 590009-590009

    • DOI

      10.3389/fcell.2020.590009

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Decreased Proliferation in the Neurogenic Niche, Disorganized Neuroblast Migration, and Increased Oligodendrogenesis in Adult Netrin-5-Deficient Mice2020

    • Author(s)
      Ikegaya Shunsuke、Iga Yurika、Mikawa Sumiko、Zhou Li、Abe Manabu、Sakimura Kenji、Sato Kohji、Yamagishi Satoru
    • Journal Title

      Frontiers in Neuroscience

      Volume: 14 Pages: 570974-570974

    • DOI

      10.3389/fnins.2020.570974

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] G ATA2 mediates the negative regulation of the prepro-thyrotropin-releasing hormone gene by liganded T3 receptor β2 in the rat hypothalamic paraventricular nucleus2020

    • Author(s)
      Kuroda Go、Sasaki Shigekazu、Matsushita Akio、Ohba Kenji、Sakai Yuki、Shinkai Shinsuke、Nakamura Hiroko Misawa、Yamagishi Satoru、Sato Kohji、Hirahara Naoko、Oki Yutaka、Ito Masahiko、Suzuki Tetsuro、Suda Takafumi
    • Journal Title

      PLOS ONE

      Volume: 15 Issue: 11 Pages: e0242380-e0242380

    • DOI

      10.1371/journal.pone.0242380

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Upregulation of Cannabinoid Receptor Type 2, but Not TSPO, in Senescence-Accelerated Neuroinflammation in Mice: A Positron Emission Tomography Study2019

    • Author(s)
      Satoru Yamagishi, Yurika Iga, Masato Nakamura, Chika Takizawa, Dai Fukumoto, Takeharu Kakiuchi, Shingo Nishiyama, Hiroyuki Ohba, Hideo Tsukada, Kohji Sato, Yasuomi Ouchi
    • Journal Title

      J Neuroinflammation .

      Volume: 16 Issue: 1 Pages: 208-208

    • DOI

      10.1186/s12974-019-1604-3

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Flrt2 Is Involved in Fine-Tuning of Osteoclast Multinucleation2019

    • Author(s)
      Jumpei Shirakawa, Noriko Takegahara, Hyunsoo Kim, Seoung Hoon Lee, Kohji Sato, Satoru Yamagishi, Yongwon Choi
    • Journal Title

      BMB Reports

      Volume: 52 Issue: 8 Pages: 514-519

    • DOI

      10.5483/bmbrep.2019.52.8.116

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Placental labyrinth formation in mice requires endothelial FLRT2/UNC5B signaling2017

    • Author(s)
      Tai-Nagara Ikue、Yoshikawa Yusuke、Numata Naoko、Ando Tomofumi、Okabe Keisuke、Sugiura Yuki、Ieda Masaki、Takakura Nobuyuki、Nakagawa Osamu、Zhou Bin、Okabayashi Koji、Suematsu Makoto、Kitagawa Yuko、Bastmeyer Martin、Sato Kohji、Klein R?diger、Navankasattusas Sutip、Li Dean Y.、Yamagishi Satoru、Kubota Yoshiaki
    • Journal Title

      Development

      Volume: 144 Pages: 2392-2401

    • DOI

      10.1242/dev.149757

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] Decreased proliferation in the neurogenic niche, disorganized neuroblast migration and increased oligodendrogenesis in adult netrin-5 deficient mice.2021

    • Author(s)
      Ikegaya S, Iga Y, Mikawa S, Zhou L, Abe M, Sakimura K, Sato K, Yamagishi S
    • Organizer
      第126回日本解剖学会総会・全国学術集会・第98回日本生理学会大会
    • Related Report
      2020 Annual Research Report
  • [Presentation] Involvement of Noggin, a novel repulsive guidance molecule, in glial scar formation of the cerebral infarction2020

    • Author(s)
      Satoru Yamagishi
    • Organizer
      New Frontiers in Neuroscience 2020
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Presentation] Nogginノックアウトマウスにおける脳梁形成について2020

    • Author(s)
      八木 亮、山岸 覚、佐藤 康二
    • Organizer
      日本解剖学会
    • Related Report
      2019 Research-status Report
  • [Presentation] Repulsive guidance molecule FLRT2 regulates social behavior2019

    • Author(s)
      Satoru Yamagishi, Fumihiro Eto, Yo shinoda, Shuhei Ogawa, Ikuko Yao, Tsuyoshi Miyakawa, Keizo Takao and Kohji Sato
    • Organizer
      Neuro2019(日本神経科学会)
    • Related Report
      2019 Research-status Report
  • [Presentation] Repulsive guidance molecule FLRT2 regulates social behavior2019

    • Author(s)
      Satoru Yamagishi, Fumihiro Eto, Yo shinoda, Shuhei Ogawa, Ikuko Yao, Tsuyoshi Miyakawa, Keizo Takao and Kohji Sato
    • Organizer
      Society for Neuroscience
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Presentation] Netrin-5ノックアウトマウスにおける成体脳神経新生について2019

    • Author(s)
      池ヶ谷俊介、山岸覚、阿部学、崎村建司、佐藤康二
    • Organizer
      日本解剖学会
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] Repulsive guidance molecule FLRT2 regulates neuronal migration and social behavior.2018

    • Author(s)
      Satoru Yamagishi, Yo shinoda, Syuhei Ogawa, Tsuyoshi Miyakawa, Keizo Takao and Kohji Sato
    • Organizer
      日本神経科学会
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] Repulsive guidance molecule FLRT2 regulates neuronal migration and social behavior.2018

    • Author(s)
      Satoru Yamagishi, Yo shinoda, Syuhei Ogawa, Tsuyoshi Miyakawa, Keizo Takao and Kohji Sato
    • Organizer
      Society for Neuroscience
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] 神経軸索ガイダンス分子FLRT2による社会性行動制御2018

    • Author(s)
      山岸覚
    • Organizer
      第123回日本解剖学会
    • Related Report
      2017 Research-status Report
  • [Presentation] Unc5Dノックアウトマウスにおける成体脳神経新生について2018

    • Author(s)
      小山夏輝、山岸覚、佐藤康二
    • Organizer
      第123回日本解剖学会
    • Related Report
      2017 Research-status Report
  • [Presentation] Netrin-5 is upregulated in the peri-infarct region after middle cerebral artery occlusion.2017

    • Author(s)
      Satoru Yamagishi, Mika Takarada, Masato Sawada, Kazunobu Sawamoto, Osamu Hori, Kohji Sato
    • Organizer
      Society for Neuroscience,
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research
  • [Presentation] Netrin-5 is upregulated in the peri-infarct region after middle cerebral artery occlusion.2017

    • Author(s)
      Satoru Yamagishi, Mika Takarada, Masato Sawada, Kazunobu Sawamoto, Osamu Hori, Kohji Sato
    • Organizer
      第60回日本神経化学会
    • Related Report
      2017 Research-status Report

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Published: 2017-04-28   Modified: 2022-01-27  

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