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Elucidation of the function of Apc gene in the formation of hippocampal neural networks using a novel three-dimensional analysis method

Research Project

Project/Area Number 18K14843
Research Category

Grant-in-Aid for Early-Career Scientists

Allocation TypeMulti-year Fund
Review Section Basic Section 46020:Anatomy and histopathology of nervous system-related
Research InstitutionFujita Health University

Principal Investigator

Onouchi Takanori  藤田医科大学, 研究推進本部 オープンファシリティセンター, 講師 (20632954)

Project Period (FY) 2018-04-01 – 2022-03-31
Project Status Completed (Fiscal Year 2021)
Budget Amount *help
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2020: ¥520,000 (Direct Cost: ¥400,000、Indirect Cost: ¥120,000)
Fiscal Year 2019: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
Fiscal Year 2018: ¥2,860,000 (Direct Cost: ¥2,200,000、Indirect Cost: ¥660,000)
KeywordsAPC / APC1638T / 海馬 / 神経細胞 / 神経ネットワーク / 光-電子相関顕微鏡法 / 組織透明化法 / APC / 神経ネットワーク形成 / 脳組織透明化法
Outline of Final Research Achievements

APC (adenomatous polyposis coli) was originally identified as a tumor suppressor protein. APC1638T mutation encodes truncated APC lacking the C-terminal domains. This mutation does not affect the β-catenin-regulating functional motifs. Accordingly, APC1638T mice are tumor-free. To determine the functional role of the C-terminus of APC in the hippocampal neural networks, we performed morphological analysis in APC1638T mice.In APC1638T mice, the hippocampal neuronal dendrites were thinner, c-Fos-positive nerve cells were lower than that in wild-type mice. APC and PSD-95 were colocalized at post-synaptic site in the hippocampus of wild-type mice, while not colocalized in APC1638T mice.

Academic Significance and Societal Importance of the Research Achievements

APCタンパク質は最初、癌抑制因子として発見されたので、腫瘍研究者の間に非常に関心が集まり、発癌に関する研究が今まで盛んに行われてきた。APCタンパク質は脳にも多く発現しているが、脳腫瘍の発生に関与していない。これまで、脳におけるAPCタンパク質の働きは、よく分かっていなかった。本研究より、海馬に発現するAPCが海馬神経ネットワーク形成に関与していることが示唆された。本研究に用いたAPC1638Tマウスは、統合失調症様行動を示す。APC1638Tマウスを使った研究は、統合失調症の発症メカニズムの解明に前進をもたらし、統合失調症の新たな治療法の開発につながると期待される。

Report

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

    (1 results)

All 2020

All Journal Article (1 results) (of which Peer Reviewed: 1 results)

  • [Journal Article] Morphological and functional abnormalities of hippocampus in APC1638T/1638T mice2020

    • Author(s)
      Li Chenguang、Onouchi Takanori、Hirayama Masaya、Sakai Kazuyoshi、Matsuda Shuji、Yamada Nami O.、Senda Takao
    • Journal Title

      Medical Molecular Morphology

      Volume: 54 Issue: 1 Pages: 31-40

    • DOI

      10.1007/s00795-020-00257-3

    • Related Report
      2020 Research-status Report
    • Peer Reviewed

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Published: 2018-04-23   Modified: 2023-01-30  

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