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Involvement of endosomal Toll-like receptors in the development of neuropathic pain

Research Project

Project/Area Number 24659827
Research Category

Grant-in-Aid for Challenging Exploratory Research

Allocation TypeSingle-year Grants
Research Field Functional basic dentistry
Research InstitutionKyushu University

Principal Investigator

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

Co-Investigator(Kenkyū-buntansha) HAYASHI Yoshinori  九州大学, 歯学研究院, 助教 (80582717)
Project Period (FY) 2012-04-01 – 2014-03-31
Project Status Completed (Fiscal Year 2013)
Budget Amount *help
¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000)
Fiscal Year 2013: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2012: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Keywords歯科薬理学 / Toll様受容体 / 神経障害性疼痛 / TOLL様受容体と慢性疼痛 / Unc93b / IFN- γ / ミクログリア
Research Abstract

3d mice have defective signaling via TLR3, TLR7 and TLR9 due to the mutation of Unc93b1. In this study, the roles of these receptors on the induction of neuropathic pain were elucidated using 3d mice. 3d mice had statistically significant higher pain threshold as comparison with that of wild-type mice. In wild-type mice, the mean expression levels of inflammatory molecules in the spinal cord were significantly increased following peripheral nerve injury. In contrast, the mean expression levels of anti-inflammatory molecules were significantly increased in the spinal cord of 3d mice following peripheral nerve injury. These observations suggest that spinal microglia of wild-type mice polarize to M1 phenotype following peripheral nerve injury through activation of TLR9. On the other hand, spinal microglia in 3d mice polarize to M2 phenotype following peripheral nerve injury, inducing resistance to neuropathic pain.

Report

(3 results)
  • 2013 Annual Research Report   Final Research Report ( PDF )
  • 2012 Research-status Report
  • Research Products

    (30 results)

All 2014 2013 2012 Other

All Journal Article (8 results) (of which Peer Reviewed: 7 results) Presentation (18 results) (of which Invited: 6 results) Book (4 results)

  • [Journal Article] Periphera1 ro1e of cathepsin S in Thl ce11-dependent transition of nerve injury-induced acute pain to a chronic pain state2014

    • Author(s)
      Xinwen Zhang,Zhou Wu,Yoshinori ayashi,Ryo Okada R,iroshi Nakanishi
    • Journal Title

      J Neurosci

      Volume: Vo1 34,No. 8 Pages: 3013-3022

    • Related Report
      2013 Final Research Report
  • [Journal Article] Peripheral role of cathepsin S in Th1 cell-dependent transition of nerve injury-induced acute pain to a chronic pain state2014

    • Author(s)
      Xinwen Zhang, Zhou Wu, Yoshinoru Hayashi, Ryo Okada R, Hiroshi Nakanishi
    • Journal Title

      J Neurosci

      Volume: 34 Pages: 3013-3022

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Leptomeningeal cells transduce peripheral macrophages inflammatory signal to microglia in response to Porphyromonas gingivalis LPS2013

    • Author(s)
      Yicong Liu, Zhou Wu, Xinwen Zhang, Junjun Ni, Weixian Yu, Yanmin Zhou, Hiroshi Nakanishi
    • Journal Title

      Mediators Inflamm

      Volume: 2013:407562 Pages: 1-11

    • DOI

      10.1155/2013/407562

    • Related Report
      2013 Annual Research Report 2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Brazilian green propolis suppresses the hypoxia-induced neuroinflammatory responses by inhibiting NF-kB activation in microglia2013

    • Author(s)
      Zhou Wu, Aiqin Zhu, Fumiko Takayama, Ryo Okada, Yicong Liu, Yuka Harada, Shizheng Wu, Hiroshi Nakanishi
    • Journal Title

      Oxid Med Cell Longev

      Volume: 2013:906726 Pages: 1-10

    • DOI

      10.1155/2013/906726

    • Related Report
      2013 Annual Research Report 2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Possible involvement of aiPLA2 in the phosphatidylserine-containing liposomes induced production of PGE2 and PGD2 in microglia2013

    • Author(s)
      Fumiko Takayama, Zhou Wu, Hong Ma HM, Okada R, Yoshinori Hayashi, Hiroshi Nakanishi
    • Journal Title

      J Neuroimmunol

      Volume: 262 Issue: 1-2 Pages: 121-124

    • DOI

      10.1016/j.jneuroim.2013.06.011

    • Related Report
      2013 Annual Research Report 2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Differential pathways for interleukin-1b production activated by chromogranin A and amyloid β in microglia2013

    • Author(s)
      Zhou Wu, Li Sun, Sadayuki Hashioka, Yu S, Schwab C, Ryo Okada, Yoshinori Hayashi, Patrick L McGeer PL, Hiroshi Nakanishi
    • Journal Title

      Neurobiol Aging

      Volume: 34 Issue: 12 Pages: 2715-2725

    • DOI

      10.1016/j.neurobiolaging.2013.05.018

    • Related Report
      2013 Annual Research Report 2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Microglial Cathepsin B Contributes to the Initiation of Peripheral Inflammation-induced Chronic Pain.2012

    • Author(s)
      S. Li, Z. Wu, Y. Hayashi, C. Peters, K. Inoue, M. Tsuda, and H. Nakanishi.
    • Journal Title

      J.Neurosci.

      Volume: 32(33) Issue: 33 Pages: 11330-42

    • DOI

      10.1523/jneurosci.0677-12.2012

    • Related Report
      2013 Final Research Report 2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Age-dependent neuroinflammatory responses and deficits in long-term potentiation in the hippocampus during systemic inflammation2012

    • Author(s)
      Liu X, Wu Z, Hayashi Y, Nakanishi H
    • Journal Title

      Neuroscience

      Volume: 216 Pages: 133-142

    • DOI

      10.1016/j.neuroscience.2012.04.050

    • Related Report
      2013 Final Research Report 2012 Research-status Report
    • Peer Reviewed
  • [Presentation] 神経障害性疹痛の慢性化におけるカテプシンSの役割2014

    • Author(s)
      張馨文、武洲、林良憲、中西博
    • Organizer
      第87回日本薬理学会年会
    • Place of Presentation
      仙台国際センター
    • Year and Date
      2014-03-19
    • Related Report
      2013 Final Research Report
  • [Presentation] Batten病モデルマウスにおける脳ベリサイトの消失と血液脳関門の破綻2013

    • Author(s)
      岡田亮、武洲、見軍軍、中西博
    • Organizer
      第66回日本薬理学会西南部会
    • Place of Presentation
      福岡大学
    • Year and Date
      2013-11-16
    • Related Report
      2013 Final Research Report
  • [Presentation] クロモグラニンA(CGA)によるミクログリアにおけるカテプシンBに依存した新規産生経路の解明2013

    • Author(s)
      武洲、中西博
    • Organizer
      第55回歯科基礎医学学術大会
    • Place of Presentation
      岡山コンベンションセンター
    • Year and Date
      2013-09-22
    • Related Report
      2013 Final Research Report
  • [Presentation] Microg1ia1 circadian c1ock contro1s diurna1 changes in synaptic strength through microg1ia-synaptic interactions2013

    • Author(s)
      中西博
    • Organizer
      シンポジウム、Neuro20l3
    • Place of Presentation
      国立京都国際会館
    • Year and Date
      2013-06-21
    • Related Report
      2013 Final Research Report
  • [Presentation] Microg1ia1 circadian c1ock contro1s microg1ia-synapse interactions in the hea1thy brain,in Symposium of"Why do microg1ia exist in the brain : As a target for treatment of neuro1ogica1 disorders"2013

    • Author(s)
      中西博
    • Organizer
      シンポジウム,第90回日本生理学会大会
    • Year and Date
      2013-03-28
    • Related Report
      2013 Final Research Report
  • [Presentation] Regu1ation of microg1ia-synapse interactions and synaptic strength by microg1ia1 circadian c1ock,in Symposium of"Ro1es of microg1ia and astrocytes in synaptic reorganization : New trends in g1ia1 research"2013

    • Author(s)
      林良憲,中西博
    • Organizer
      シンポジウム,第86回日本薬理学会年会
    • Year and Date
      2013-03-21
    • Related Report
      2013 Final Research Report
  • [Presentation] Microglial circadian clock controls microglia-synapse interactions in the healthy brain2013

    • Author(s)
      林 良憲, 中西 博
    • Organizer
      第86回日本薬理学会年会、シンポジウム:Roles of microglia and astrocytes in synaptic reotganization: New trends in glial research
    • Place of Presentation
      福岡
    • Related Report
      2012 Research-status Report
    • Invited
  • [Presentation] Microglial circadian clock controls microglia-synapse interactions in the healthy brain2013

    • Author(s)
      中西 博
    • Organizer
      第90回日本生理学会大会、シンポジウム:Why do microglia exist in the brain: As a terget for treatment of neurological disorders
    • Place of Presentation
      東京
    • Related Report
      2012 Research-status Report
    • Invited
  • [Presentation] ミクログリアの産生するカテプシン群の慢性疹痛における役割2012

    • Author(s)
      中西博
    • Organizer
      平成年度生理研研究会「痛み研究の新たな展開」
    • Place of Presentation
      岡崎(教育講演)
    • Year and Date
      2012-12-13
    • Related Report
      2013 Final Research Report
  • [Presentation] NMDAレセプターとミクログリア2012

    • Author(s)
      中西博,林良憲
    • Organizer
      CINP・NP20l2合同年会,シンポジウム: NMDAレセプター神経疾患の分子病態を探る
    • Place of Presentation
      宇都宮
    • Year and Date
      2012-10-20
    • Related Report
      2013 Final Research Report
  • [Presentation] ミクログリアの電気生理学的解析2012

    • Author(s)
      中西博
    • Organizer
      包括型脳科学研究推進支援ネットワーク・夏のワークショップ,「グリア機能解析jチユートリアル
    • Place of Presentation
      仙台
    • Year and Date
      2012-07-27
    • Related Report
      2013 Final Research Report
  • [Presentation] NMDAレセプターとミクログリア, CINP・NP2012合同年会, シンポジウム: NMDAレセプター神経疾患の分子病態を探る2012

    • Author(s)
      中西 博
    • Organizer
      CINP・NP2012合同年会
    • Place of Presentation
      宇都宮
    • Related Report
      2012 Research-status Report
    • Invited
  • [Presentation] ミクログリアの産生するカテプシン群の慢性疼痛における役割2012

    • Author(s)
      中西 博
    • Organizer
      平成24年度生理研研究会「痛み研究の新たな展開」
    • Place of Presentation
      岡崎
    • Related Report
      2012 Research-status Report
    • Invited
  • [Presentation] Microglial circadian clock controls microglia-synapse interactions through P2Y12 receptors and cathepsin S expression2012

    • Author(s)
      中西 博
    • Organizer
      The 15th Annual Meeting of the Korean Society for Brain and Neural Science in Symposium of Glial Neuroscience
    • Place of Presentation
      ソウル
    • Related Report
      2012 Research-status Report
    • Invited
  • [Presentation] Microglial circadian clock controls diurnal changes in synaptic strength through microglia-synaptic interactions

    • Author(s)
      中西 博
    • Organizer
      Neuro2013
    • Place of Presentation
      国立京都国際会館
    • Related Report
      2013 Annual Research Report
    • Invited
  • [Presentation] クロモグラニンA(CGA)によるミクログリアにおけるカテプシンBに依存した新規産生経路の解明

    • Author(s)
      武 洲、中西 博
    • Organizer
      第55回歯科基礎医学学術大会
    • Place of Presentation
      岡山コンベンションセンター
    • Related Report
      2013 Annual Research Report
  • [Presentation] Batten病モデルマウスにおける脳ペリサイトの消失と血液脳関門の破綻、第66回日本薬理学会西南部会

    • Author(s)
      岡田 亮、武 洲、倪 軍軍、中西 博
    • Organizer
      第66回日本薬理学会西南部会
    • Place of Presentation
      福岡大学
    • Related Report
      2013 Annual Research Report
  • [Presentation] 神経障害性疼痛の慢性化におけるカテプシンSの役割

    • Author(s)
      張 馨文、武 洲、林 良憲、中西 博
    • Organizer
      第87回日本薬理学会年会
    • Place of Presentation
      仙台国際センター
    • Related Report
      2013 Annual Research Report
  • [Book] TNF-α signaling and cathepsin B, In: Tumor Necrosis Factor: Structure, Enzyme Regulation and Role in Health and Disease2013

    • Author(s)
      Zhou Wu, Hiroshi Nakanishi
    • Total Pages
      15
    • Publisher
      Nova Science Publishers, Inc.
    • Related Report
      2012 Research-status Report
  • [Book] BK+ channels contribute to the cellular activation of microglia : a big channel in small glia, In: Glial Cells: Embryonic Development, Types/Functions and Role in Disease2013

    • Author(s)
      Yoshinori Hayashi, Hiroshi Nakanishi
    • Total Pages
      18
    • Publisher
      Nova Science Publishers, Inc.
    • Related Report
      2012 Research-status Report
  • [Book] Microglia-aging and pain: Microglial cathepsin B-dependent IL-1β production, In: Interleukin-1: Genetics, Inflammatory Mechanisms and Role in Disease2013

    • Author(s)
      Hiroshi Nakanishi, Zhou Wu
    • Total Pages
      12
    • Publisher
      Nova Science Publishers, Inc.
    • Related Report
      2012 Research-status Report
  • [Book] NMDAレセプターとミクログリア:ミクログリアのシナプス可塑性ならびにシナプス再編への関与2013

    • Author(s)
      林 良憲、中西 博
    • Total Pages
      26
    • Publisher
      日本神経精神薬理学雑誌
    • Related Report
      2012 Research-status Report

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Published: 2013-05-31   Modified: 2019-07-29  

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