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Development of fluorescence imaging technology for central catecholamines

Research Project

Project/Area Number 17H04029
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field General pharmacology
Research InstitutionThe University of Tokyo

Principal Investigator

Hirose Kenzo  東京大学, 大学院医学系研究科(医学部), 教授 (00292730)

Project Period (FY) 2017-04-01 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥17,940,000 (Direct Cost: ¥13,800,000、Indirect Cost: ¥4,140,000)
Fiscal Year 2019: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2018: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2017: ¥8,190,000 (Direct Cost: ¥6,300,000、Indirect Cost: ¥1,890,000)
Keywordsカテコラミン / シナプス / 蛍光イメージング
Outline of Final Research Achievements

The research aimed at developing fluorescence probes for visualization of the spatiotemporal dynamics of catecholamines in the brain, which are important neurotransmitters that control brain functions. In order to develop catecholamine-binding domain for fluorescence probes, we decided to obtain anti-catecholamine antibodies and convert them to single-chain fragments. We performed molecular design and organic synthesis of catecholamine derivatives and provided them for the production of immunoconjugates. A large number of hybridomas were obtained after treatment of mice with the conjugates, and antibodies binding to catecholamines were found through subsequent screening. However, a problem with their binding selectivity to physiological catecholamines has also been revealed. The findings obtained in this research are expected to be useful for future development of promising fluorescent probes.

Academic Significance and Societal Importance of the Research Achievements

脳内カテコラミンを可視化する蛍光プローブの開発により、いつどこでカテコラミンが上昇するのかを生きた動物の脳において可視化が実現されるようになる。カテコラミンの関与する神経機能の解析にとって今後非常に重要なツールとして役立つと考えられる。特に、カテコラミンの関与する神経機能を時空間的コンテクストで理解を提供できる点で疾病の理解、創薬を目指す上でも大きな意義を持つ。本研究で得た知見は、今後の有望な蛍光プローブの開発に役立つと期待できる。

Report

(4 results)
  • 2019 Annual Research Report   Final Research Report ( PDF )
  • 2018 Annual Research Report
  • 2017 Annual Research Report
  • Research Products

    (20 results)

All 2020 2019 2018 Other

All Journal Article (2 results) (of which Peer Reviewed: 2 results,  Open Access: 1 results) Presentation (16 results) (of which Int'l Joint Research: 4 results,  Invited: 2 results) Remarks (2 results)

  • [Journal Article] The Altered Supramolecular Structure of Dopamine D2 Receptors in Disc1-deficient Mice.2018

    • Author(s)
      Onishi T, Sakamoto H, Namiki S, Hirose K
    • Journal Title

      Sci Rep.

      Volume: 8 Issue: 1 Pages: 1692-1692

    • DOI

      10.1038/s41598-018-20090-0

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Synaptic weight set by Munc13-1 supramolecular assemblies.2018

    • Author(s)
      Sakamoto H, Ariyoshi T, Kimpara N, Sugao K, Taiko I, Takikawa K, Asanuma D, Namiki S, Hirose K.
    • Journal Title

      Nat Neurosci.

      Volume: 21 Issue: 1 Pages: 41-49

    • DOI

      10.1038/s41593-017-0041-9

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed
  • [Presentation] Quantal glutamate release organized by supramolecular assembly at presynaptic terminals2020

    • Author(s)
      Kenzo Hirose
    • Organizer
      第97回日本生理学会大会
    • Related Report
      2019 Annual Research Report
  • [Presentation] Optical measurement of glutamate release from multiple ribbon-type synapses at the terminal of goldfish retinal bipolar cell2020

    • Author(s)
      大島知子、坂本寛和 、並木繁行 、廣瀬謙造 、立花政夫 、鷹合秀輝
    • Organizer
      第97回日本生理学会大会
    • Related Report
      2019 Annual Research Report
  • [Presentation] Visualization of Ca2+ release and filling mechanisms in the endoplasmic reticulum of astrocytes2020

    • Author(s)
      大久保洋平、飯野正光、廣瀬謙造
    • Organizer
      第93回日本薬理学会年会
    • Related Report
      2019 Annual Research Report
  • [Presentation] Establishment of a new method for long-term single-molecule fluorescence imaging and its application to synaptic molecules2020

    • Author(s)
      小林新九郎、大久大久保洋平、並木繁行、浅沼大祐、廣瀬謙造保洋平、並木繁行、浅沼大祐、廣瀬謙造
    • Organizer
      第93回日本薬理学会年会
    • Related Report
      2019 Annual Research Report
  • [Presentation] Development of a novel chemical tag tool for caicium imaging by near-infrared fluorescence2020

    • Author(s)
      磯野有希、浅沼大祐、大久保洋平、並木繁行、廣瀬謙造
    • Organizer
      第93回日本薬理学会年会
    • Related Report
      2019 Annual Research Report
  • [Presentation] Molecular organization underlying presynaptic function2019

    • Author(s)
      Kenzo Hirose
    • Organizer
      Core-to-Core Program "Understanding Synapses-from molecules to function"
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Synaptic release sites studied by g;utamate imaging techniques and supreresolution microscopy2019

    • Author(s)
      Kenzo Hirose
    • Organizer
      Ribbon Synapses Symposium 2019
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] 大脳皮質における細胞外ATP動態のin vivo蛍光イメージング2019

    • Author(s)
      北島奈美、瀧川健司、関谷敬、並木繁行、飯野正光、廣瀬謙造
    • Organizer
      第140回日本薬理学会関東部会
    • Related Report
      2019 Annual Research Report
  • [Presentation] アストロサイトにおけるIP3受容体2型非依存性Ca2+放出2019

    • Author(s)
      大久保 洋平、金丸 和典、鈴木 純二、小林 憲太、廣瀬 謙造、飯野 正光
    • Organizer
      第92回 日本薬理学会年会(日本、大阪)
    • Related Report
      2018 Annual Research Report
  • [Presentation] Development of turn-on fluorescent tag system for live-cell imaging2019

    • Author(s)
      Sin Ying Yip, Shigeyuki Namiki, Daisuke Asanuma, Kenzo Hirose
    • Organizer
      第92回 日本薬理学会年会(日本、大阪)
    • Related Report
      2018 Annual Research Report
  • [Presentation] 近赤外蛍光in vivoイメージングのためのケミカルタグツールの開発2019

    • Author(s)
      小島 佑介、浅沼 大祐、岡本 紘幸、並木 繁行、廣瀬 謙造
    • Organizer
      第92回 日本薬理学会年会(日本、大阪)
    • Related Report
      2018 Annual Research Report
  • [Presentation] 近赤外蛍光in vivoイメージングのためのケミカルタグツールの開発2019

    • Author(s)
      小島 佑介、浅沼 大祐、岡本 紘幸、並木 繁行、廣瀬 謙造
    • Organizer
      日本化学会 第99春季年会(日本、兵庫)
    • Related Report
      2018 Annual Research Report
  • [Presentation] 近赤外蛍光in vivoイメージングのためのケミカルタグツールの開発2019

    • Author(s)
      小島 佑介、浅沼 大祐、岡本 紘幸、並木 繁行、廣瀬 謙造
    • Organizer
      日本薬学会 第139年会(日本、千葉)
    • Related Report
      2018 Annual Research Report
  • [Presentation] Development of a tag-probe based cell labeling technique in vivo fluorescence imaging2018

    • Author(s)
      Hiroyuki Okamoto, Daisuke Asanuma, Shigeyuki Namiki, Kenzo Hirose
    • Organizer
      WCP2018(日本、京都)
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Development live cell superresolution microscopy based on a novel fluorescence switching technology2018

    • Author(s)
      Shigeyuki Namiki, Daisuke Asanuma, Kenzo Hirose
    • Organizer
      WCP2018(日本、京都)
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] アストロサイトにおけるIP3受容体2型非依存性Ca2+放出2018

    • Author(s)
      大久保 洋平、金丸 和典、廣瀬 謙造、飯野 正光
    • Organizer
      生理研研究会「シグナル動態の可視化と操作に基づく多階層機能解析の新展開」(日本、愛知)
    • Related Report
      2018 Annual Research Report
  • [Remarks] 東京大学大学院医学系研究科機能生物学専攻細胞分子薬理学分野

    • URL

      http://www.pharmacol.m.u-tokyo.ac.jp/

    • Related Report
      2019 Annual Research Report 2018 Annual Research Report
  • [Remarks]

    • URL

      http://www.neurobiol.m.u-tokyo.ac.jp/

    • Related Report
      2017 Annual Research Report

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Published: 2017-04-28   Modified: 2021-02-19  

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