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Imaging analysis of neuronal circuit for dissecting brain function and dysfunction

Research Project

Project/Area Number 21K07580
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 InstitutionNational Institutes for Quantum Science and Technology

Principal Investigator

Shimojo Masafumi  国立研究開発法人量子科学技術研究開発機構, 量子医科学研究所 脳機能イメージング研究部, 研究統括 (20455348)

Project Period (FY) 2021-04-01 – 2024-03-31
Project Status Completed (Fiscal Year 2023)
Budget Amount *help
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2023: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2022: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2021: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Keywords光イメージング / PETイメ―ジング / 回路 / 炎症 / 認知症 / イメージング / 回路病態 / 多細胞 / 神経回路 / 生体脳イメージング
Outline of Research at the Start

認知症を呈する神経疾患において回路破綻に起因する発症カスケードが提唱されており、こうした病態を画像評価しその制御法を確立する事は極めて重要性が高い。本研究課題では、脳深部回路を構成する多細胞活動を脳局所と全脳で生体脳イメージングする事を実現し、同細胞群の活動により調節される回路の制御基盤の理解とそれらが破綻するメカニズム解明に取り組む事を通じて、イメージング創薬へと繋がる技術基盤の確立を目指す。

Outline of Final Research Achievements

In this research, we aimed to establish an in vivo imaging platform to analyze multicellular activities in neuronal circuits for dissecting brain function and dysfunction. We first developed an experimental system to visualize the cellular activities of neurons and astrocytes in the cerebral cortex using calcium imaging-based analysis. In addition, we also established PET reporter imaging techniques in combination with systemic injection of AAVs with serotype PHPeB which enables to conduct of whole brain macro-imaging of cellular distributions and activities. Finally, utilizing a mouse model for tauopathies, we examined the abnormal cellular activities in the brains of these animals.

Academic Significance and Societal Importance of the Research Achievements

本課題の成果として、ニューロンやアストロサイト細胞活動の相互作用を脳局所と全脳でイメージングを基軸とした手法により調べる研究プラットフォームが構築された。また、タウ蓄積を呈する認知症モデルマウス脳において、回路を構成する細胞群の中で特に抑制性ニューロンやグリア細胞の機能に障害を生じるている可能性が明らかとなった。

Report

(4 results)
  • 2023 Annual Research Report   Final Research Report ( PDF )
  • 2022 Research-status Report
  • 2021 Research-status Report
  • Research Products

    (20 results)

All 2023 2022 2021

All Journal Article (7 results) (of which Int'l Joint Research: 5 results,  Peer Reviewed: 7 results,  Open Access: 6 results) Presentation (13 results) (of which Int'l Joint Research: 2 results,  Invited: 3 results)

  • [Journal Article] Selective dysfunction of fast-spiking inhibitory interneurons and disruption of perineuronal nets in a tauopathy mouse model.2023

    • Author(s)
      Kudo T, Takuwa H, Takahashi M, Urushihata T, Shimojo M, Sampei K, Yamanaka M, Tomita Y, Sahara N, Suhara T, Higuchi M
    • Journal Title

      iScience

      Volume: 26 Issue: 4 Pages: 106342-106342

    • DOI

      10.1016/j.isci.2023.106342

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] A quantitative in vivo imaging platform for tracking pathological tau depositions and resultant neuronal death in a mouse model2022

    • Author(s)
      Kimura Taeko、Ono Maiko、Seki Chie、Sampei Kazuaki、Shimojo Masafumi、Kawamura Kazunori、Zhang Ming-Rong、Sahara Naruhiko、Takado Yuhei、Higuchi Makoto
    • Journal Title

      European Journal of Nuclear Medicine and Molecular Imaging

      Volume: 49 Issue: 13 Pages: 4298-4311

    • DOI

      10.1007/s00259-022-05898-3

    • Related Report
      2022 Research-status Report
    • Peer Reviewed
  • [Journal Article] Central role for p62/SQSTM1 in the elimination of toxic tau species in a mouse model of tauopathy2022

    • Author(s)
      Ono Maiko、Komatsu Masaaki、Ji Bin、Takado Yuhei、Shimojo Masafumi、Minamihisamatsu Takeharu、Warabi Eiji、Yanagawa Toru、Matsumoto Gen、Aoki Ichio、Kanaan Nicholas M.、Suhara Tetsuya、Sahara Naruhiko、Higuchi Makoto
    • Journal Title

      Aging Cell

      Volume: 21 Issue: 7

    • DOI

      10.1111/acel.13615

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] A first-in-human study of 11C-MTP38, a novel PET ligand for phosphodiesterase 72021

    • Author(s)
      Kubota Manabu、Seki Chie、Kimura Yasuyuki、Takahata Keisuke、Shimada Hitoshi、Takado Yuhei、Matsuoka Kiwamu、Tagai Kenji、Sano Yasunori、Yamamoto Yasuharu、Okada Maki、Kikuchi Tatsuya、Ichise Masanori、Kawamura Kazunori、Zhang Ming-Rong、Higuchi Makoto
    • Journal Title

      European Journal of Nuclear Medicine and Molecular Imaging

      Volume: 41 Issue: 11 Pages: 2928-2943

    • DOI

      10.1177/0271678x211004150

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] MRS-measured glutamate versus GABA reflects excitatory versus inhibitory neural activities in awake mice2021

    • Author(s)
      Takado Yuhei、Takuwa Hiroyuki、Sampei Kazuaki、Urushihata Takuya、Takahashi Manami、Shimojo Masafumi、Uchida Shoko、Nitta Nobuhiro、Shibata Sayaka、Nagashima Keisuke、Ochi Yoshihiro、Ono Maiko、Maeda Jun、Tomita Yutaka、Sahara Naruhiko、Near Jamie、Aoki Ichio、Shibata Kazuhisa、Higuchi Makoto
    • Journal Title

      Journal of Cerebral Blood Flow & Metabolism

      Volume: 42 Issue: 1 Pages: 197-212

    • DOI

      10.1177/0271678x211045449

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] A genetically targeted reporter for PET imaging of deep neuronal circuits in mammalian brains2021

    • Author(s)
      Shimojo M、Ono M、Takuwa H、Mimura K、Nagai Y、Fujinaga M、Kikuchi T、Okada M、Seki C、Tokunaga M、Maeda J、Takado Y、Takahashi M、Minamihisamatsu T、Zhang M‐R、Tomita Y、Suzuki N、Maximov A、Suhara T、Minamimoto T、Sahara N、Higuchi M
    • Journal Title

      The EMBO Journal

      Volume: 40 Issue: 22

    • DOI

      10.15252/embj.2021107757

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Neurodegenerative processes accelerated by protein malnutrition and decelerated by essential amino acids in a tauopathy mouse model2021

    • Author(s)
      Sato H、Takado Y、Toyoda S、Tsukamoto-Yasui M、Minatohara K、Takuwa H、Urushihata T、Takahashi M、Shimojo M、Ono M、Maeda J、Orihara A、Sahara N、Aoki I、Karakawa S、Isokawa M、Kawasaki N、Kawasaki M、Ueno S、Kanda M、Nishimura M、Suzuki K、Mitsui A、Nagao K、Kitamura A、Higuchi M
    • Journal Title

      Science Advances

      Volume: 7 Issue: 43 Pages: 1-11

    • DOI

      10.1126/sciadv.abd5046

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] 脳疾患モデル動物を用いたPET画像解析2023

    • Author(s)
      下條 雅文
    • Organizer
      第66回日本神経化学会大会
    • Related Report
      2023 Annual Research Report
    • Invited
  • [Presentation] In vivo assessment of progressive astrogliosis in rTg4510 tauopathy animal brains2023

    • Author(s)
      Shimojo Masafumi, Minamihisamatsu Takeharu, Takahiro Shimizu, Uchida Shoko, Takahashi Manami, Takuwa Hiroyuki, Matsushita Yumi, Yanai Rin, Minatohara Keiichiro, Zhang Ming-Rong, Sahara Naruhiko, Higuchi Makoto
    • Organizer
      SfN2023
    • Related Report
      2023 Annual Research Report
    • Int'l Joint Research
  • [Presentation] In vivo assessment of progressive astrogliosis in rTg4510 tauopathy animal brains2023

    • Author(s)
      Shimojo Masafumi, Minamihisamatsu Takeharu, Takahiro Shimizu, Uchida Shoko, Takahashi Manami, Takuwa Hiroyuki, Matsushita Yumi, Yanai Rin, Minatohara Keiichiro, Zhang Ming-Rong, Sahara Naruhiko, Higuchi Makoto
    • Organizer
      第50回 内藤カンファレンス
    • Related Report
      2023 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Molecular profiles of inflammatory astrocyte in rTg4510 tauopathy animal brains2023

    • Author(s)
      Shimojo Masafumi, Minamihisamatsu Takeharu, Takahiro Shimizu, Uchida Shoko, Takahashi Manami, Takuwa Hiroyuki, Matsushita Yumi, Yanai Rin, Minatohara Keiichiro, Zhang Ming-Rong, Sahara Naruhiko, Higuchi Makoto
    • Organizer
      第46回日本神経科学会
    • Related Report
      2023 Annual Research Report
  • [Presentation] 認知症モデル動物脳における炎症病態の画像解析2022

    • Author(s)
      下條 雅文
    • Organizer
      タウ研究会2022
    • Related Report
      2022 Research-status Report
  • [Presentation] In vivo assessment of progressive astrogliosis in the pathophysiological cascade of rTg4510 tauopathy animal brains2022

    • Author(s)
      Shimojo Masafumi, Minamihisamatsu Takeharu, Manami Takahashi, Takuwa Hiroyuki, Matsushita Yumi, Yanai Rin, Keiichiro Minatohara, Zhang Ming-Rong, Sahara Naruhiko, Higuchi Makoto
    • Organizer
      第45回 日本分子生物学会
    • Related Report
      2022 Research-status Report
  • [Presentation] In vivo assessment of progressive astrogliosis in the pathophysiological cascade of rTg4510 tauopathy animal brains2022

    • Author(s)
      Shimojo Masafumi, Minamihisamatsu Takeharu, Manami Takahashi, Takuwa Hiroyuki, Matsushita Yumi, Yanai Rin, Keiichiro Minatohara, Zhang Ming-Rong, Sahara Naruhiko, Higuchi Makoto
    • Organizer
      Neuro2022
    • Related Report
      2022 Research-status Report
  • [Presentation] ecDHFRイメージング用の遺伝子レポーターPETトレーサー[18F]FHP-TMPの開発2022

    • Author(s)
      大久保 崇之, 下條 雅文, 小野 麻衣子, 藤永 雅之, 小川 政直, 念垣 信樹, 永井 裕司, 南本 敬史, 樋口 真人, 張 明栄
    • Organizer
      第62回日本核医学会学術総会
    • Related Report
      2022 Research-status Report
  • [Presentation] 脳深部回路を可視化するPETレポーターイメージング技術2022

    • Author(s)
      下條 雅文
    • Organizer
      第24回 日本ヒト脳機能マッピング学会
    • Related Report
      2021 Research-status Report
    • Invited
  • [Presentation] Genetically targeted PET reporter imaging of deep neuronal circuit in the mammalian brain2021

    • Author(s)
      Shimojo Masafumi、Ono Maiko、Takuwa Hiroyuki、Mimura Koki、Nagai Yuji、Fujinaga Masayuki、Kikuchi Tatsuya、Okada Maki、Seki Chie、Tokunaga Masaki、Maeda Jun、Takado Yuhei、Takahashi Manami、Minamihisamatsu Takeharu、Zhang Ming‐Rong、Tomita Yutaka、Suzuki Norihiro、Maximov Anton、Higuchi Makoto
    • Organizer
      第44回 日本分子生物学会年会
    • Related Report
      2021 Research-status Report
  • [Presentation] Genetically targeted PET reporter imaging of deep neuronal circuit in the mammalian brain2021

    • Author(s)
      Shimojo Masafumi、Ono Maiko、Takuwa Hiroyuki、Mimura Koki、Nagai Yuji、Fujinaga Masayuki、Kikuchi Tatsuya、Okada Maki、Seki Chie、Tokunaga Masaki、Maeda Jun、Takado Yuhei、Takahashi Manami、Minamihisamatsu Takeharu、Zhang Ming‐Rong、Tomita Yutaka、Suzuki Norihiro、Maximov Anton、Higuchi Makoto
    • Organizer
      第64回日本神経化学会大会
    • Related Report
      2021 Research-status Report
  • [Presentation] Genetically encoded reporter for PET monitoring of neuronal ensemble activities in the deep brain circuit2021

    • Author(s)
      Shimojo Masafumi、Ono Maiko、Takuwa Hiroyuki、Mimura Koki、Nagai Yuji、Fujinaga Masayuki、Kikuchi Tatsuya、Okada Maki、Seki Chie、Tokunaga Masaki、Maeda Jun、Takado Yuhei、Takahashi Manami、Minamihisamatsu Takeharu、Zhang Ming‐Rong、Tomita Yutaka、Suzuki Norihiro、Maximov Anton、Higuchi Makoto
    • Organizer
      第44回日本神経科学大会
    • Related Report
      2021 Research-status Report
  • [Presentation] タウ病態モデルマウスにおける脳回路障害とその画像描出2021

    • Author(s)
      下條 雅文
    • Organizer
      タウ研究会議
    • Related Report
      2021 Research-status Report
    • Invited

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Published: 2021-04-28   Modified: 2025-01-30  

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