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Analysis of Porphyromonas gingivalis-induced neuroinflammation by multi-photon imaging of microglia dynamics

Research Project

Project/Area Number 15K15684
Research Category

Grant-in-Aid for Challenging Exploratory Research

Allocation TypeMulti-year Fund
Research Field Functional basic dentistry
Research InstitutionKyushu University

Principal Investigator

Nakanishi Hiroshi  九州大学, 歯学研究院, 教授 (20155774)

Research Collaborator TAKAYAMA Fumiko  
Project Period (FY) 2015-04-01 – 2017-03-31
Project Status Completed (Fiscal Year 2016)
Budget Amount *help
¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000)
Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2015: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Keywordsジンジバリス菌 / ミクログリア / 生体蛍光イメージング / 突起伸展 / P2Y6受容体 / 生体イメージング
Outline of Final Research Achievements

In the present study, we have first shown that cortical microglia extend their processes towards focally injected Porphyromonas gingivalis (P. gingivalis). The focally injected P. gingivalis-induced microglial process extension was significantly increased during the light (sleeping) phase than the dark (waking) phase. In contrast, focally injected ATP-induced microglial process extension was significantly increased during the dark phase than the light phase. Furthermore, in contrast to P2Y12 receptor-mediated mechanism of ATP-induced microglial process extension, P. gingivalis-mediated microglial process extension was mediated by P2Y6 receptors. Therefore, P. gingivalis infiltrated in the brain parenchyma may induce the secretion of UDP from microglia at the site of infiltration, UDP, in turn, induces the process extension of neighboring microglia.

Report

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

    (26 results)

All 2017 2016 2015

All Journal Article (11 results) (of which Int'l Joint Research: 6 results,  Peer Reviewed: 11 results,  Open Access: 9 results,  Acknowledgement Compliant: 8 results) Presentation (15 results) (of which Int'l Joint Research: 4 results,  Invited: 5 results)

  • [Journal Article] Overexpression of cathepsin E interferes with neuronal differentiation of P19 embryonal teratocarcinoma cells by degradation of N-cadherin.2017

    • Author(s)
      Harada Y, Takayama F, Tanabe K, Ni J, Hayashu Y, Yamamoto K, Wu Z, Nakanishi H
    • Journal Title

      Cell Mol Neurobiol

      Volume: 37 Pages: 437-443

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] An EP2 agonist facilitates NMDA-induced outward currents and inhibits dendritic beading through activation of BK channels in mouse cortical neurons.2016

    • Author(s)
      Hayashi Y, Morinaga S, Liu X, Zhang J, Wu Z, Yokoyama T, Nakanishi H
    • Journal Title

      Mediators Inflamm

      Volume: 2016 Pages: 5079597-5079597

    • DOI

      10.1155/2016/5079597

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] BK channels in microglia are required for2016

    • Author(s)
      Yoshinori Hayashi, Saori Morinaga, Jing Zhang, Yasushi Satoh, Andrea Meredith, Takahiro Nakata, Zhou Wu, Shinichi Kohsaka, Kazuhide Inoue, Hiroshi Nakanishi
    • Journal Title

      Nature communications

      Volume: 7 Issue: 1 Pages: 11697-11697

    • DOI

      10.1038/ncomms11697

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Diurnal dynamic behavior of microglia in response to infected bacteria through the UDP-P2Y6 receptor system.2016

    • Author(s)
      Takayama F, Hayashi Y, Wu Z, Liu Y, Nakanishi H.
    • Journal Title

      Sci Rep

      Volume: 6 Issue: 1 Pages: 30006-30006

    • DOI

      10.1038/srep30006

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Cathepsin B regulates collagen expression by fibroblasts via prolonging TLR2/NF-kB activation.2016

    • Author(s)
      Li X, Wu Z, Ni J, Liu Y, Meng J, Yu W, Nakanishi H, Zhou Y
    • Journal Title

      Oxid Med Cell Longev

      Volume: 2016 Issue: 1 Pages: 7894247-7894247

    • DOI

      10.1155/2016/7894247

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Nutrient, microglia aging, and brain aging.2016

    • Author(s)
      Wu Z, Yu J, Zhu A, Nakanishi H
    • Journal Title

      Oxid Med Cell Longev

      Volume: 2016 Issue: 1 Pages: 7498528-7498528

    • DOI

      10.1155/2016/7498528

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Cathepsin D deficiency induces oxidative damage in brain pericytes and impairs the blood-brain barrier2015

    • Author(s)
      Yoshinori Hayashi Y, Yuka Koga, Xinwen Zhang, Christoph Peters, Yanagawa Y, Zhou Wu, Takeshi Yokoyama, Hiroshi Nakanishi
    • Journal Title

      Molecular and Cellular Neuroscience

      Volume: 64 Pages: 51-60

    • DOI

      10.1016/j.mcn.2014.12.002

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] The Critical Role of Proteolytic Relay through Cathepsins B and E in the Phenotypic Change of Microglia/Macrophage2015

    • Author(s)
      XJunjun Ni, Zhou Wu, Christoph Peterts, Kenji Yamamoto, Hong Qing, and Hiroshi Nakanishi2015
    • Journal Title

      Journal of Neuroscience

      Volume: 35 Issue: 36 Pages: 12488-12501

    • DOI

      10.1523/jneurosci.1599-15.2015

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] The downwardspiralofperiodontitisanddiabetesinAlzheimer's disease: Extendinghealthylifeexpectancythroughoralhealth2015

    • Author(s)
      Hiroshi Nakanishi, Zhou WU
    • Journal Title

      Journal of Oral Biosciences

      Volume: 57 Issue: 3 Pages: 139-142

    • DOI

      10.1016/j.job.2015.05.002

    • Related Report
      2015 Research-status Report
    • Peer Reviewed
  • [Journal Article] Lessons from Microglia Aging for the Link between Inflammatory Bone Disorders and Alzheimer’s Disease2015

    • Author(s)
      Zhou Wu, Hiroshi Nakanishi
    • Journal Title

      Journal of Immunology Research

      Volume: 2015 Pages: 471342-471342

    • DOI

      10.1155/2015/471342

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] The Neuroprotective Effects of Ratanasampil on Oxidative Stress-Mediated Neuronal Damage in Human Neuronal SH-SY5Y Cells2015

    • Author(s)
      Aiqin Zhu, Zhou Wu, Jie Meng, Patrick L. McGeer, Yi Zhu, Hiroshi Nakanishi, and Shizheng Wu
    • Journal Title

      Oxidative Medicine and Cellular Longevity

      Volume: 2015 Pages: 1-10

    • DOI

      10.1155/2015/792342

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Presentation] Gingipains induce microglial migration through activation of protease-activated receptor-2 (PAR-2)2017

    • Author(s)
      Yicong Liu, Zhou Wu, Hiroshi Nakanishi
    • Organizer
      95tth Annual Meeting of International Association for Dental Research (IADR2017)
    • Place of Presentation
      サンフランシスコ(USA)
    • Year and Date
      2017-03-24
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 歯周病と認知機能:増悪機序の解明と今後の展望2017

    • Author(s)
      武 洲、中西 博
    • Organizer
      第90回日本薬理学会年会(年会企画シンポジウム:口腔ブレインサイエンスに学ぶ健康長寿)
    • Place of Presentation
      長崎新聞文化ホール(長崎)
    • Year and Date
      2017-03-17
    • Related Report
      2016 Annual Research Report
    • Invited
  • [Presentation] The critical roles of gingipains in cell migration and inflammatory response of microglia through activation of protease-activated receptor-2 (PAR-2)2017

    • Author(s)
      Yicong Liu, Zhou Wu, Tomoko Kadowaki, Hiroshi Nakanishi
    • Organizer
      第90回日本薬理学会年会
    • Place of Presentation
      長崎ブリックホール(長崎)
    • Year and Date
      2017-03-17
    • Related Report
      2016 Annual Research Report
  • [Presentation] IL-10 plays a pivotal role in anti-inflammatory effects of Pheum tanguticum in activated microglia2017

    • Author(s)
      Jie Meng, Junjun Ni, Zhou Wu, Aiquin Zhu, Hiroshi Nakanishi
    • Organizer
      第90回日本薬理学会年会
    • Place of Presentation
      長崎ブリックホール(長崎)
    • Year and Date
      2017-03-17
    • Related Report
      2016 Annual Research Report
  • [Presentation] Possible involvement of cathepsin H in the negative regulation of T cell activation in experimental autoimmune encepalomyelitis (EAE)2016

    • Author(s)
      Ryo Okada, Yuka Harada, Zhou Wu, Ryo Yamasaki, Hiroshi Nakanishi,
    • Organizer
      第21回グリア研究会
    • Place of Presentation
      千里ライフサイエンスセンター(大阪)
    • Year and Date
      2016-12-03
    • Related Report
      2016 Annual Research Report
  • [Presentation] Microglia fascilitate brain aging and cognitive imairment through cathepsin B-dependent oxidative and inflammatory responses,2016

    • Author(s)
      Junjun Ni, Zhou Wu, Hiroshi Nakanishi
    • Organizer
      第21回グリア研究会
    • Place of Presentation
      千里ライフサイエンスセンター(大阪)
    • Year and Date
      2016-12-03
    • Related Report
      2016 Annual Research Report
  • [Presentation] ミクログリアにおけるIL-10産生分泌を介したRheum tanguticumの抗炎症作用2016

    • Author(s)
      孟ジェイ、武 洲、門脇知子、中西 博
    • Organizer
      第69回日本薬理学会西南部会
    • Place of Presentation
      松山大学(愛媛)
    • Year and Date
      2016-11-26
    • Related Report
      2016 Annual Research Report
  • [Presentation] Arg-ならびにLys-gingipainによるprotease-activated receptor-2(PAR-2)の活性化を介したミクログリアの細胞遊走誘導2016

    • Author(s)
      劉 訳聡、武 洲、朱 愛琴、中西 博
    • Organizer
      第69回日本薬理学会西南部会
    • Place of Presentation
      松山大学(愛媛)
    • Year and Date
      2016-11-26
    • Related Report
      2016 Annual Research Report
  • [Presentation] Pathological roles of microglial cathepsins in chronic pain2016

    • Author(s)
      Hiroshi Nakanishi
    • Organizer
      XVth Symposium on Proteases, Inhibitors and Biological Control
    • Place of Presentation
      ポートローズ、スロベニア
    • Year and Date
      2016-09-30
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] 歯周病菌感染による脳内アルツハイマー様病態の誘発メカニズム2016

    • Author(s)
      武 洲、中西 博
    • Organizer
      第58回歯科基礎医学会学術大会(サテライトシンポジウム:健康長寿社会を目指す口腔ブレインサイエンスの最前線)
    • Place of Presentation
      札幌コンベンションセンター(札幌)
    • Year and Date
      2016-08-24
    • Related Report
      2016 Annual Research Report
    • Invited
  • [Presentation] ATPならびにPorphyromonas gingivalis(PG)局所注入により惹起されるミクログリア突起の集積とその日内変化に関する生体イメージング解析2015

    • Author(s)
      髙山扶美子、林 良憲、武 洲、中西
    • Organizer
      第57回歯科基礎医学会学術大会
    • Place of Presentation
      朱鷺メッセ新潟
    • Year and Date
      2015-09-11
    • Related Report
      2015 Research-status Report
  • [Presentation] Periodontitis and Alzheimer’s disease (AD) (1): A possible role of leptomeninges in transduction of inflammatory signals from peripheral macrophages to microglia in the response to lipopolyssacharide from Porphyromonas gingivalis2015

    • Author(s)
      Yicong Liu、Zhou Wu、 Hiroshi Nakanishi
    • Organizer
      第57回歯科基礎医学会学術大会
    • Place of Presentation
      朱鷺メッセ新潟
    • Year and Date
      2015-09-11
    • Related Report
      2015 Research-status Report
  • [Presentation] Periodontitis and Alzheimer’s disease (AD) (2): Critical roles of cathepsin B in AD-like phenotypes in middle-aged mice following chronic systemic treatment with lipopolyssacharide from Porphyromonas gingivalis2015

    • Author(s)
      Junjun Ni、Zhou Wu、 Hiroshi Nakanishi
    • Organizer
      第57回歯科基礎医学会学術大会
    • Place of Presentation
      朱鷺メッセ新潟
    • Year and Date
      2015-09-11
    • Related Report
      2015 Research-status Report
  • [Presentation] Lessons from cathepsin deficient mice on human brain diseases2015

    • Author(s)
      Hiroshi Nakanishi
    • Organizer
      The 4th International Conference and Exhibition on Neurology & Therapeutics
    • Place of Presentation
      Holiday Inn Rome Aurelia
    • Year and Date
      2015-07-25
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] Modulator actions of microglial cathepsins in brain diseases2015

    • Author(s)
      Hiroshi Nakanishi
    • Organizer
      Cold Spring Harbor Asia(CSHA Conference 2015): New Insights into Glia Function & Dysfunction
    • Place of Presentation
      Worldhotel Grand Dushulake Suzhou
    • Year and Date
      2015-06-22
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research / Invited

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Published: 2015-04-16   Modified: 2018-03-22  

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