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Organelle dynamics for fate determination of injured neurons

Research Project

Project/Area Number 16H05117
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field General anatomy (including histology/embryology)
Research InstitutionNagoya University

Principal Investigator

Kiyama Hiroshi  名古屋大学, 医学系研究科, 教授 (00192021)

Co-Investigator(Renkei-kenkyūsha) KIRYU-SEO Sumiko  名古屋大学, 大学院医学系研究科, 准教授 (70311529)
KONISHI Hiroyuki  名古屋大学, 大学院医学系研究科, 講師 (90448746)
Project Period (FY) 2016-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥17,550,000 (Direct Cost: ¥13,500,000、Indirect Cost: ¥4,050,000)
Fiscal Year 2018: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2017: ¥5,980,000 (Direct Cost: ¥4,600,000、Indirect Cost: ¥1,380,000)
Fiscal Year 2016: ¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000)
Keywordsミトコンドリア / 神経損傷 / 軸索再生 / 軸索障害 / 運動神経 / オルガネラ / 神経再生 / 神経変性 / 軸索損傷 / ATF3 / 解剖学 / 運動ニューロン / 細胞・組織 / 脳神経疾患
Outline of Final Research Achievements

We have investigated significances of organelle dynamics which are observed in response to nerve injury. We used the BAC transgenic mice, which express mitochondria labelling GFP and Cre recombinase protein simultaneously and specifically in nerve injured neurons in response to nerve injury. After nerve injury the mitochondria in injured nerve became smaller and moved quicker, although the mitochondrial size in cell soma was not changed. This morphological alteration of mitochondria would be important for delivering mitochondria to regenerating nerve tip. The deletion of Dpr1, which is a responsible molecule for the mitochondrial fission, induced mitochondrial enlargement, and the Drp1 deleted motor neurons died quickly in response to nerve injury.

Academic Significance and Societal Importance of the Research Achievements

運動神経損傷後に生じるオルガネラ動態の変化が、損傷神経細胞の生存や再生に重要な役割を果たしていることが明らかになった。特にミトコンドリアは融合と分裂を繰り返すことで機能を維持しているが、分裂の欠損により神経損傷に対する耐性が失われることが明らかになった。これらの結果は、オルガネラ動態の異常に起因する神経変性疾患の変性メカニズムの解明に繋がることが予想され、これら疾患の治療法開発への貢献が期待される。本研究の成果は、神経変性疾患以外にも外傷後の運動神経再生や神経障害性疼痛の治療法開発にも新たな知見を提供すると考えられる。

Report

(4 results)
  • 2018 Annual Research Report   Final Research Report ( PDF )
  • 2017 Annual Research Report
  • 2016 Annual Research Report
  • Research Products

    (12 results)

All 2019 2018 2017 2016

All Journal Article (6 results) (of which Int'l Joint Research: 3 results,  Peer Reviewed: 5 results,  Open Access: 4 results,  Acknowledgement Compliant: 3 results) Presentation (6 results) (of which Int'l Joint Research: 2 results,  Invited: 5 results)

  • [Journal Article] Mitochondrial behavior during axon regeneration/degeneration in vivo,2019

    • Author(s)
      Kiryu-Seo S, Kiyama H
    • Journal Title

      Neurosci Res

      Volume: 139 Pages: 42-47

    • DOI

      10.1016/j.neures.2018.08.014

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] 損傷神経細胞にみられる分子とオルガネラの再編とその意義2019

    • Author(s)
      木山博資、小西博之、桐生寿美子
    • Journal Title

      生体の科学

      Volume: 70 Pages: 58-62

    • Related Report
      2018 Annual Research Report
  • [Journal Article] Three-dimensional analysis of somatic mitochondrial dynamics in fission-deficient injured motor neurons using FIB/SEM2017

    • Author(s)
      Tamada H, Kiryu-Seo S, Hosokawa H, Ohta K, Ishihara N, Nomura M, Mihara K, Nakamura KI, Kiyama H
    • Journal Title

      Jounral of Comparative Neurology

      Volume: 印刷中 Issue: 11 Pages: 1-14

    • DOI

      10.1002/cne.24213

    • NAID

      120006343671

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Phospholipid localization implies microglial morphology and function via Cdc42 in vitro2017

    • Author(s)
      Kyohei Tokizane, Hiroyuki Konishi, Kumiko Makide, Hiroki Kawana, Shinichi Nakamuta, Kozo Kaibuchi, Tomohiko Ohwada, Junken Aoki, Hiroshi Kiyama
    • Journal Title

      Glia

      Volume: 65 Issue: 5 Pages: 740-755

    • DOI

      10.1002/glia.23123

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Distinct types of protease systems are involved in homeostasis regulation of mitochondrial morphology via balanced fusion and fission.2016

    • Author(s)
      S. Saita, T. Ishihara, M.Maeda, S. Iemura, T. Natsume, K. Mihara and N. Ishihara.
    • Journal Title

      Genes Cells.

      Volume: 21 Issue: 1 Pages: 408-424

    • DOI

      10.1038/srep28331

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Mitochondria-associated membrane collapse is a common pathomechanism in SIGMAR1- and SOD1-linked ALS.2016

    • Author(s)
      Watanabe S, Ilieva H, Tamada H, Nomura H, Komine O, Endo F, Jin S, Mancias P, Kiyama H, *Yamanaka K.
    • Journal Title

      EMBO Molecular Medicine

      Volume: 8 Issue: 12 Pages: 1421-1437

    • DOI

      10.15252/emmm.201606403

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Presentation] Mitochondria in the regenerating and degenerating neurons after nerve injury2018

    • Author(s)
      Kiryu-Seo, Kiyama
    • Organizer
      APICA
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] セルダイナミクス・オルガネラダイナミクスをみる2017

    • Author(s)
      木山博資
    • Organizer
      第44回皮膚かたち研究学術集会
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] 新たな技術による末梢神経再生メカニズム研究の新展開2017

    • Author(s)
      木山博資
    • Organizer
      第28回日本末梢神経学会学術集会
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] Lipids regulate microglial morphology and function2016

    • Author(s)
      Kiyama H
    • Organizer
      Cold Spring Harbor Asia Conferences, New insights into Glia function & Dysfunction
    • Place of Presentation
      Suzhou, China
    • Year and Date
      2016-12-05
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] 先天性関節拘縮症の原因遺伝子としてのDINEと軸索再生におけるミトコンドリアダイナミクス2016

    • Author(s)
      木山博資, 松本早紀子、永田健一、玉田宏美、時實恭平、小西博之、桐生寿美子
    • Organizer
      第17回ORIGIN 神経科学研究会
    • Place of Presentation
      まつや千千(福井県・あわら市)
    • Year and Date
      2016-08-27
    • Related Report
      2016 Annual Research Report
  • [Presentation] 消化管平滑筋・腸管神経系・ICC の形態学的解析2016

    • Author(s)
      玉田宏美、木山博資
    • Organizer
      第58回日本平滑筋学会
    • Place of Presentation
      東北医科薬科大学(宮城県・仙台市)
    • Year and Date
      2016-08-17
    • Related Report
      2016 Annual Research Report
    • Invited

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Published: 2016-04-21   Modified: 2020-03-30  

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