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How are synaptic adhesion molecules involved in functional gastrointestinal disorders?

Research Project

Project/Area Number 20K21605
Research Category

Grant-in-Aid for Challenging Research (Exploratory)

Allocation TypeMulti-year Fund
Review Section Medium-sized Section 53:Organ-based internal medicine and related fields
Research InstitutionNagasaki University

Principal Investigator

Aruga Jun  長崎大学, 医歯薬学総合研究科(医学系), 教授 (10232076)

Project Period (FY) 2020-07-30 – 2022-03-31
Project Status Completed (Fiscal Year 2021)
Budget Amount *help
¥6,370,000 (Direct Cost: ¥4,900,000、Indirect Cost: ¥1,470,000)
Fiscal Year 2021: ¥3,120,000 (Direct Cost: ¥2,400,000、Indirect Cost: ¥720,000)
Fiscal Year 2020: ¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000)
Keywords機能性消化管障害 / シナプス接着分子 / 機能性ディスペプシア / 過敏性腸症候群 / 遺伝子改変マウス / 脳腸相関 / 不安障害 / 抑うつ障害 / 疾患モデル動物
Outline of Research at the Start

機能性消化管障害とは、慢性の腹部症状を呈するにもかかわらず、検査によって器質的疾患(がん、潰瘍など)が認められない機能性の消化器疾患群であり、機能性ディスペプシアや過敏性腸症候群が含まれる。病態の理解に「脳腸相関」の重要性が明確になっているが、未だ不明な点が多い。申請者らは、中枢神経系と腸管神経系に発現するシナプス接着分子「LRR膜貫通タンパク質群」を欠損するマウスでは神経学的症状の他に消化管機能が変化している可能性を見いだした。LRR膜タンパク質遺伝子変異マウスを対象にして、多角的な解析を行うことにより、「LRR膜タンパク質が脳腸相関の生理的な調節にどのように関わるのか」を明らかにする。

Outline of Final Research Achievements

In our previous studies, we observed mild body weight loss in neuronal Leucine-rich repeat (LRR) proteins-deficient mice that show various neurological signs similar to anxiety, depression, and sensory dysfunction. In this study, we hypothesized that some LRR proteins are invovled in regulating brain-gut interaction. Based on the hypothesis, we carried out detailed analysis on the funtion and molecular marker changes in LRR proteins-deficient mice. We collected critical data including the body weight changes in LRR protein-deficient mice, features of their feeding behaviors, and contractility of their intestines. To further verify above hypothesis, we started generating conditional knockout for some LRR protein-coding genes.

Academic Significance and Societal Importance of the Research Achievements

本研究の完遂により、以下の点が期待できる。
(1)脳腸相関の実体を分子レベルから、より良く理解することができる。(2)機能性消化管障害の治療法改善に貢献できる。(3)機能性消化管障害と不安・抑うつとの関係性について、新たな仮説を検証でき、新たな研究展開につながる。(4)この研究の過程で作成された遺伝子改変動物は成果発表後、公共の実験動物リソース維持機関で維持され、医学生物学研究に広く利用されるようになる。

Report

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

    (4 results)

All 2022 2021

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

  • [Journal Article] Lrtm2 controls protein sorting in the striatal projection system and its deficiency causes disturbances in motor responses and monoamine dynamics2022

    • Author(s)
      Misato Ichise, Kazuto Sakoori, Kei-ichi Katayama, Naoko Morimura, Kazuyuki Yamada, Hiroki Ozawa, Hayato Matsunaga, Minoru Hatayama, Jun Aruga
    • Journal Title

      Frontiers in Molecular Neuroscience

      Volume: - Pages: 856315-856315

    • DOI

      10.3389/fnmol.2022.856315

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Characterization of a Primate Blood-Brain Barrier Co-Culture Model Prepared from Primary Brain Endothelial Cells, Pericytes and Astrocytes2021

    • Author(s)
      Watanabe Daisuke、Nakagawa Shinsuke、Morofuji Yoichi、Toth Andrea E.、Vastag Monika、Aruga Jun、Niwa Masami、Deli Maria A.
    • Journal Title

      Pharmaceutics

      Volume: 13 Issue: 9 Pages: 1484-1484

    • DOI

      10.3390/pharmaceutics13091484

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Trans-Synaptic Regulation of Metabotropic Glutamate Receptors by Elfn Proteins in Health and Disease2021

    • Author(s)
      Matsunaga H, Aruga J
    • Journal Title

      Front Neural Circuits

      Volume: 15 Pages: 634875-634875

    • DOI

      10.3389/fncir.2021.634875

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Dysregulation of erythropoiesis and altered erythroblastic NMDA receptor-mediated calcium influx in Lrfn2-deficient mice2021

    • Author(s)
      Maekawa R, Muto H, Hatayama M, Aruga J
    • Journal Title

      PLoS One

      Volume: 16 Issue: 1 Pages: e0245624-e0245624

    • DOI

      10.1371/journal.pone.0245624

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access

URL: 

Published: 2020-08-03   Modified: 2023-01-30  

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