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Functional analysis of serotonergic innervation using a visualisation model to challenge paediatric intestinal peristalsis

Research Project

Project/Area Number 18K08554
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 55010:General surgery and pediatric surgery-related
Research InstitutionOsaka Medical and Pharmaceutical University

Principal Investigator

Tomiyama Hideki  大阪医科薬科大学, 医学部, 准教授 (20298433)

Co-Investigator(Kenkyū-buntansha) 谷口 高平  大阪医科薬科大学, 医学部, 講師 (70779686)
内山 和久  大阪医科薬科大学, 医学部, 名誉教授 (80232867)
Project Period (FY) 2018-04-01 – 2024-03-31
Project Status Completed (Fiscal Year 2023)
Budget Amount *help
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2020: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2019: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Keywordsゼブラフィッシュ / 腸管神経系 / 蠕動 / セロトニン / セロトニン神経 / 蠕動不全
Outline of Final Research Achievements

To elucidate the serotonergic neuronal functions within the enteric nervous system and the pathophysiology of intestinal dysmotility, we have established an experimental model using zebrafish, which remain transparent during development and differentiation, allowing for internal observation. Analysis of intestinal motility using the SONY SI8000 Cell Motion System revealed that antegrade and retrograde peristalsis are formed with distinct contraction vectors. Moreover, we discovered that the hcn4 gene, which is expressed in cardiac pacemaker cells, regulates retrograde peristalsis. Additionally, we successfully developed an hcn4 gene knockout model and observed a reduction in retrograde peristalsis.

Academic Significance and Societal Importance of the Research Achievements

ヒルシュプルング病や腸管神経節細胞僅少症などに代表される腸管蠕動不全症は希少疾患であり、癌研究などと比較して研究が遅れている分野である。その克服のためには可能な限り実際の生体内を模倣した良質な実験系モデルが必要である。よってゲノム編集が容易で、胎生変化に加え、透明で全腸の観察が生きた同一個体内で可能なゼブラフィッシュモデルが最適であると考え研究に着手した。神経発生に関与するセロトニン神経の機能を本モデルで解析することは、胎生期に腸管神経系の発達異常をきたす疾患の病態解明に繋がる。

Report

(7 results)
  • 2023 Annual Research Report   Final Research Report ( PDF )
  • 2022 Research-status Report
  • 2021 Research-status Report
  • 2020 Research-status Report
  • 2019 Research-status Report
  • 2018 Research-status Report
  • Research Products

    (3 results)

All 2020 2019 2018

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

  • [Journal Article] Gastrointestinal Neurons Expressing HCN4 Regulate Retrograde Peristalsis2020

    • Author(s)
      Fujii Kensuke、Nakajo Koichi、Egashira Yoshihiro、Yamamoto Yasuhiro、Kitada Kazuya、Taniguchi Kohei、Kawai Masaru、Tomiyama Hideki、Kawakami Koichi、Uchiyama Kazuhisa、Ono Fumihito
    • Journal Title

      Cell Reports

      Volume: 30 Issue: 9 Pages: 2879-2888

    • DOI

      10.1016/j.celrep.2020.02.024

    • Related Report
      2020 Research-status Report 2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] The role of HCN4-positive cells in the gastrointestinal development and motility of zebrafish2019

    • Author(s)
      藤井研介、中條浩一、川上浩一、江頭良明、山本耕裕、谷口高平、河合英、富山英紀、内山和久、小野富三人
    • Organizer
      第9回アジア・オセアニア生理学会連合大会
    • Related Report
      2019 Research-status Report 2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] 腸管でのHCN4発現ニューロンの同定と、消化管運動における役割2018

    • Author(s)
      藤井研介、中條浩一、川上浩一、江頭良明、山本耕裕、河合英、富山英紀、内山和久、小野富三人
    • Organizer
      第111回 近畿生理学談話会
    • Related Report
      2018 Research-status Report

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Published: 2018-04-23   Modified: 2025-01-30  

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