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Impairment of Golgi pH homeostasis cause neurodegeneration

Research Project

Project/Area Number 15K18961
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field General anatomy (including histology/embryology)
Research InstitutionJuntendo University

Principal Investigator

Sou Yu-shin  順天堂大学, 医学部, 助教 (60576221)

Project Period (FY) 2015-04-01 – 2018-03-31
Project Status Completed (Fiscal Year 2017)
Budget Amount *help
¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000)
Fiscal Year 2016: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2015: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
KeywordsGPHR / ゴルジ体 / 神経変性 / 小脳回路 / プルキンエ細胞 / バスケット細胞 / 酸性環境 / pH
Outline of Final Research Achievements

To address the importance of the Golgi lumenal pH homeostasis in brain and neuronal circuit level, we took advantage of GPHR conditional knock-out mice. Brain specific GPHR deficient mice exhibit tremor symptoms, and histological analysis revealed that cerebral cortex and hippocampal CA1 neuron shedding, accumulation of TUNEL positive neurons in the surface layer, fragmentation of Golgi in neuron. These results indicated that brain specific GPHR-deficient mice develop neurodegenerative disease. We also found that disruption of synapse due to axonal degeneration of basket cells and remodeling of neuronal circuits to Purkinje cells occurred in cerebellar inhibitory circuit specific-GPHR deficient mice.

Report

(4 results)
  • 2017 Annual Research Report   Final Research Report ( PDF )
  • 2016 Research-status Report
  • 2015 Research-status Report
  • Research Products

    (4 results)

All 2017 2016

All Journal Article (1 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 1 results) Presentation (3 results)

  • [Journal Article] Linear ubiquitination of cytosolic Salmonella Typhimurium activates NF-κB and restricts bacterial proliferation2017

    • Author(s)
      van Wijk Sjoerd J. L.、Fricke Franziska、Herhaus Lina、Gupta Jalaj、H?tte Katharina、Pampaloni Francesco、Grumati Paolo、Kaulich Manuel、Sou Yu-shin、Komatsu Masaaki、Greten Florian R.、Fulda Simone、Heilemann Mike、Dikic Ivan
    • Journal Title

      Nat Microbiol.

      Volume: 2 Issue: 7 Pages: 17066-17066

    • DOI

      10.1038/nmicrobiol.2017.66

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Presentation] ゴルジ体酸性環境不全に起因する病態発症機序の解明2017

    • Author(s)
      曽友深、角田宗一郎、前田祐輔、木下タロウ、渡辺雅彦、崎村健司、内山安男、小池正人
    • Organizer
      第122回日本解剖学会総会
    • Place of Presentation
      長崎大学
    • Year and Date
      2017-03-30
    • Related Report
      2016 Research-status Report
  • [Presentation] An essential role for GPHR in cerebellar neurons2017

    • Author(s)
      曽 友深、角田 宗一郎、前田 祐輔、木下 タロウ、内山安男、小池 正人
    • Organizer
      ConBio2017
    • Related Report
      2017 Annual Research Report
  • [Presentation] ゴルジ体の形態異常に起因する神経病態発症機序の解明2016

    • Author(s)
      曽高 友深、角田 宗一郎、前田 祐輔、木下 タロウ、渡辺 雅彦、崎村 建司、内山 安男、小池 正人
    • Organizer
      日本解剖学会
    • Place of Presentation
      福島県ビックパレットふくしま
    • Year and Date
      2016-03-28
    • Related Report
      2015 Research-status Report

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Published: 2015-04-16   Modified: 2019-03-29  

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