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Clarification of mechanism of neurodegeneration in prion diseases by neuron-specific transcriptome analysis in brain

Research Project

Project/Area Number 17K14954
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field Nerve anatomy/Neuropathology
Research InstitutionHokkaido University

Principal Investigator

Takeshi Yamasaki  北海道大学, 獣医学研究院, 助教 (70709881)

Project Period (FY) 2017-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2018: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2017: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
Keywordsプリオン病 / 神経変性 / トランスクリプトーム / 神経変性疾患 / 神経細胞死 / 脳神経疾患 / 神経科学
Outline of Final Research Achievements

Neurodegeneration in prion diseases is considered to be caused by generation of an abnormal isoform of prion protein (PrPSc) within neurons in the brains of animals affected by prions. In this study, we approached the molecular basis of mechanism of the neurodegeneration by comprehensive gene expression analysis of degenerating neurons in prion-infected mouse brains. Transcriptome analysis on the thalamus, where severe neuronal loss was observed, revealed that expression of apoptosis-related genes such as a stress-responsive transcription factor, ATF3, were up-regulated by prion-infection. The results suggest that neurodegeneration in prion diseases might be caused by the activation of signaling pathway involved in ATF3 molecules.

Academic Significance and Societal Importance of the Research Achievements

神経変性疾患の治療法開発のためには異常タンパクの増殖に起因する神経変性機構を解明することが最重要課題である。本研究で、プリオン病モデルマウスの脳内で変性過程にある神経細胞の遺伝子発現プロファイルが得られたことから、神経変性機構を理解する上で価値の高い情報を提供できた。また、プリオン感染マウスの脳内神経細胞で、アポトーシス関連因子の発現上昇を伴ってATF3が発現誘導されたことから、ATF3分子が変性過程にある神経細胞のマーカーとなることが示された。今後、ATF3分子を中心とした解析を行うことで、詳細な神経変性機構の解明、ひいてはATF3関連分子を標的とした治療法開発につながることが期待される。

Report

(3 results)
  • 2018 Annual Research Report   Final Research Report ( PDF )
  • 2017 Research-status Report
  • Research Products

    (6 results)

All 2018 2017

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

  • [Journal Article] Retrograde transport by clathrin-coated vesicles is involved in intracellular transport of PrPSc in persistently prion-infected cells2018

    • Author(s)
      Yamasaki T, Suzuki A, Hasebe R, Horiuchi M.
    • Journal Title

      Scientific Reports

      Volume: 8 Issue: 1 Pages: 12241-12241

    • DOI

      10.1038/s41598-018-30775-1

    • NAID

      120006539249

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Flow cytometric detection of PrPSc in neurons and glial cells from prion-infected mouse brains2018

    • Author(s)
      Yamasaki T, Suzuki A, Hasebe R, Horiuchi M.
    • Journal Title

      Journal of Virology

      Volume: 92 Issue: 1

    • DOI

      10.1128/jvi.01457-17

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] 定型BSEおよび非定型BSEプリオンに感染したマウスの脳のトランスクリプトーム解析2018

    • Author(s)
      山崎剛士、岩丸祥史、鈴木章夫、長谷部理絵、堀内基広
    • Organizer
      第161回日本獣医学会学術集会
    • Related Report
      2018 Annual Research Report
  • [Presentation] Comparison of intracerebral spread of abnormal isoform of prion protein between three rodent prion strains2018

    • Author(s)
      Takeshi YAMASAKI, Akio SUZUKI, Rie HASEBE and Motohiro HORIUCHI
    • Organizer
      Asian Pacific Prion Symposium 2018
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Comparison of intracerebral spread of abnormal isoform of prion protein between three rodent prion strains2018

    • Author(s)
      Takeshi YAMASAKI, Akio SUZUKI, Rie HASEBE and Motohiro HORIUCHI
    • Organizer
      第66回日本ウイルス学会学術集会
    • Related Report
      2018 Annual Research Report
  • [Presentation] Characterization of gene expression profiles in brains of mice infected with typical and atypical BSEs2017

    • Author(s)
      Takeshi Yamasaki, Yoshifumi Iwamaru, Yuichi Matsuura, Minori Kuroda, Rie Hasebe, Hiroyuki Okada and Motohiro Horiuchi
    • Organizer
      Asia Pacific Prion Symposium 2017
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research

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Published: 2017-04-28   Modified: 2020-03-30  

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