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Effects of a DAP12-mediated signal on microglial activation after injury

Research Project

Project/Area Number 16K07055
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Neurochemistry/Neuropharmacology
Research InstitutionNagoya University

Principal Investigator

Konishi Hiroyuki  名古屋大学, 医学系研究科, 助教 (90448746)

Project Period (FY) 2016-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2018: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2016: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Keywordsグリア / ミクログリア / 神経炎症 / 疼痛 / アロディニア / ミクログリアマーカー / TREM2 / DAP12 / 炎症 / マーカー / 神経損傷 / サイトカイン / 再生医学 / 神経障害性疼痛
Outline of Final Research Achievements

DAP12 is considered to work as a signal transduction chain of some ligand-binding receptors in microglia. Our study, using allodynia model of mice, revealed that DAP12 can regulate microglial activity both positively and negatively after injury. When DAP12 makes complex with TREM2, TREM2/DAP12 promotes microglial pro-inflammatory responses after injury, whereas Siglec-H/DAP12 complex suppresses. Furthermore, we demonstrated Siglec-H as a microglia-specific marker that discriminates microglia from brain macrophages and CNS-infiltrating monocytes.

Academic Significance and Societal Importance of the Research Achievements

シグナル伝達鎖DAP12は、異なるリガンド認識鎖(TREM2またはSiglec-H)と複合体を形成することにより、ミクログリアの活性化を正/負両方に制御することを見出した。DAP12を介するシグナルの適切な制御により、神経損傷後のミクログリアの性質を神経保護的に転換できる可能性が期待される。また、本研究により示したSiglec-Hの発現特異性は、今後のミクログリア研究において有益な情報になると考えられる。

Report

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

    (33 results)

All 2019 2018 2017 2016 Other

All Journal Article (12 results) (of which Int'l Joint Research: 3 results,  Peer Reviewed: 12 results,  Open Access: 9 results,  Acknowledgement Compliant: 4 results) Presentation (18 results) (of which Int'l Joint Research: 1 results) Remarks (3 results)

  • [Journal Article] GPR34 in spinal microglia exacerbates neuropathic pain in mice2019

    • Author(s)
      Sayo Akira、Konishi Hiroyuki、Kobayashi Masaaki、Kano Kuniyuki、Kobayashi Hiroki、Hibi Hideharu、Aoki Junken、Kiyama Hiroshi
    • Journal Title

      Journal of Neuroinflammation

      Volume: 16 Issue: 1 Pages: 23-33

    • DOI

      10.1186/s12974-019-1458-8

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Dual functions of microglia in the formation and refinement of neural circuits during development2019

    • Author(s)
      Konishi H, Kiyama H, Ueno M
    • Journal Title

      Int J Developmental Neuroscience

      Volume: 印刷中 Issue: 1 Pages: 18-25

    • DOI

      10.1016/j.ijdevneu.2018.09.009

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Branched Sialylated <i>N</i>-glycans Are Accumulated in Brain Synaptosomes and Interact with Siglec-H2018

    • Author(s)
      M. Handa-Narumi, T. Yoshimura, H. Konishi, Y. Fukata, Y. Manabe, K. Tanaka, G.-m. Bao, H. Kiyama, K. Fukase, K. Ikenaka
    • Journal Title

      Cell Structure and Function

      Volume: 43 Issue: 2 Pages: 141-152

    • DOI

      10.1247/csf.18009

    • NAID

      130007439439

    • ISSN
      0386-7196, 1347-3700
    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Microglial TREM2/DAP12 Signaling: A Double-Edged Sword in Neural Diseases2018

    • Author(s)
      Konishi Hiroyuki、Kiyama Hiroshi
    • Journal Title

      Frontiers in Cellular Neuroscience

      Volume: 12:206

    • DOI

      10.3389/fncel.2018.00206

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Lack of Fgf18 causes abnormal clustering of motor nerve terminals at the neuromuscular junction with reduced acetylcholine receptor clusters2018

    • Author(s)
      Ito Kenyu、Ohkawara Bisei、Yagi Hideki、Nakashima Hiroaki、Tsushima Mikito、Ota Kyotaro、Konishi Hiroyuki、Masuda Akio、Imagama Shiro、Kiyama Hiroshi、Ishiguro Naoki、Ohno Kinji
    • Journal Title

      Sceintific Reports

      Volume: 8 Issue: 1 Pages: 434-434

    • DOI

      10.1038/s41598-017-18753-5

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Agonists for G-protein-coupled receptor 84 (GPR84) alter cellular morphology and motility but do not induce pro-inflammatory responses in microglia2017

    • Author(s)
      Wei Li、Tokizane Kyohei、Konishi Hiroyuki、Yu Hua-Rong、Kiyama Hiroshi
    • Journal Title

      Journal of Neuroinflammation

      Volume: 14 Issue: 1 Pages: 198-198

    • DOI

      10.1186/s12974-017-0970-y

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Siglec-H is a microglia-specific marker that discriminates microglia from CNS-associated macrophages and CNS-infiltrating monocytes2017

    • Author(s)
      Konishi Hiroyuki、Kobayashi Masaaki、Kunisawa Taikan、Imai Kenta、Sayo Akira、Malissen Bernard、Crocker Paul R.、Sato Katsuaki、Kiyama Hiroshi
    • Journal Title

      Glia

      Volume: 65 Issue: 12 Pages: 1927-1943

    • DOI

      10.1002/glia.23204

    • NAID

      120006375875

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [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
      2016 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Exposure to diphtheria toxin during the juvenile period impairs both inner and outer hair cells in C57BL/6 mice2017

    • Author(s)
      Konishi H, Ohgami N, Matsushita A, Kondo Y, Aoyama Y, Kobayashi M, Nagai T, Ugawa S, Yamada K, Kato M, Kiyama H
    • Journal Title

      Neuroscience

      Volume: 印刷中 Pages: 15-23

    • DOI

      10.1016/j.neuroscience.2017.03.028

    • NAID

      120006331816

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Phenylbutazone induces expression of MBNL1 and suppresses formation of MBNL1-CUG RNA foci in a mouse model of myotonic dystrophy2016

    • Author(s)
      1.Chen G, Masuda A, Konishi H, Ohkawara B, Ito M, Kinoshita M, Kiyama H, Matsuura T, Ohno K.
    • Journal Title

      Sci Rep

      Volume: 6 Issue: 1 Pages: 25317-25317

    • DOI

      10.1038/srep25317

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] R-spondin 2 promotes acetylcholine receptor clustering at the neuromuscular junction via Lgr5.2016

    • Author(s)
      Nakashima H., Ohkawara B., Ishigaki S., Fukudome T., Ito K., Tsushima M., Konishi H., Okuno T., Yoshimura T., Ito M., Masuda A., Sobue G., Kiyama H., Ishiguro N., Ohno K.
    • Journal Title

      Sci Rep

      Volume: 22 Issue: 1 Pages: 28512-28512

    • DOI

      10.1038/srep28512

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] TREM2/DAP12 Signal Elicits Proinflammatory Response in Microglia and Exacerbates Neuropathic Pain2016

    • Author(s)
      Kobayashi M, Konishi H, Sayo A, Takai T, Kiyama H
    • Journal Title

      J Neurosci

      Volume: 36(43) Issue: 43 Pages: 11138-11150

    • DOI

      10.1523/jneurosci.1238-16.2016

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Presentation] Astrocytic phagocytic activity compensates for microglial dysfunction2019

    • Author(s)
      Hiroyuki Konishi
    • Organizer
      第11回Nagoyaグローバルリトリート
    • Related Report
      2018 Annual Research Report
  • [Presentation] ミクログリアの貪食能低下はアストロサイトにより補完される2019

    • Author(s)
      小西博之、佐藤克明、木山博資
    • Organizer
      第124回日本解剖学会総会・全国学術集会
    • Related Report
      2018 Annual Research Report
  • [Presentation] GPR34はミクログリアにおける炎症性反応を惹起し神経障害性疼痛を増悪させる2018

    • Author(s)
      佐世暁、小西博之、小林正明、日比英晴、青木淳賢、木山博資
    • Organizer
      第40回日本疼痛学会
    • Related Report
      2018 Annual Research Report
  • [Presentation] ミクログリア除去モデルマウスにおけるミクログリア残骸のアストロサイトによる貪食2018

    • Author(s)
      小西博之、岡本峻幸、佐藤克明、木山博資
    • Organizer
      第40回日本生物学的精神医学会・第61回日本神経化学会大会 合同年会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 脳シナプトソームに集積している枝分かれしたシアル酸化N結合型糖鎖はシグレックHと相互作用する2018

    • Author(s)
      吉村武、半田麻衣、小西博之、深田優子、真鍋良幸、田中克典、Guangming Bao、木山博資、深瀬浩一、池中一裕
    • Organizer
      第40回日本生物学的精神医学会・第61回日本神経化学会大会 合同年会
    • Related Report
      2018 Annual Research Report
  • [Presentation] ミクログリア除去時に現れるアストロサイトの貪食能2018

    • Author(s)
      小西博之、木山博資
    • Organizer
      第8回生理学研究所・名古屋大学医学系研究科 合同シンポジウム
    • Related Report
      2018 Annual Research Report
  • [Presentation] 脊髄後角のミクログリアに発現する GPR34 は神経障害性疼痛を悪化させる2018

    • Author(s)
      佐世暁、小西博之、小林正明、日比英晴、青木淳賢、木山博資
    • Organizer
      第8回生理学研究所・名古屋大学医学系研究科 合同シンポジウム
    • Related Report
      2018 Annual Research Report
  • [Presentation] ミクログリア除去時に現れるアストロサイトの貪食能2018

    • Author(s)
      小西博之、佐藤克明、木山博資
    • Organizer
      第78回日本解剖学会中部支部学術集会
    • Related Report
      2018 Annual Research Report
  • [Presentation] Phagocytic clearance of microglial debris by astrocytes in microglial depletion model mice2018

    • Author(s)
      小西博之、佐藤克明、木山博資
    • Organizer
      第22回グリア研究会
    • Related Report
      2018 Annual Research Report
  • [Presentation] Siglec-Hのミクログリアマーカーとしての有用性と機能2018

    • Author(s)
      小西博之、小林正明、佐藤克明、木山博資
    • Organizer
      第123回日本解剖学会総会・全国学術集会
    • Related Report
      2017 Research-status Report
  • [Presentation] Siglec-H is a specific marker for microglia in mice2017

    • Author(s)
      小西博之、小林正明、佐藤克明、木山博資
    • Organizer
      第60回日本神経化学会大会
    • Related Report
      2017 Research-status Report
  • [Presentation] ミクログリアマーカーSiglec-Hの発現特性と機能2017

    • Author(s)
      小西博之、木山博資
    • Organizer
      第7回名古屋大学医学系研究科・生理学研究所合同シンポジウム
    • Related Report
      2017 Research-status Report
  • [Presentation] ミクログリアマーカーSiglec-Hの発現特性と機能2017

    • Author(s)
      小西博之、小林正明、佐藤克明、木山博資
    • Organizer
      第77回日本解剖学会中部支部学術集会
    • Related Report
      2017 Research-status Report
  • [Presentation] Microglial debris are phagocytosed by astrocytes under absence of functional microglia2017

    • Author(s)
      小西博之、佐藤克明、木山博資
    • Organizer
      第22回グリア研究会
    • Related Report
      2017 Research-status Report
  • [Presentation] TREM2/DAP12を介するミクログリア活性化は神経障害性疼痛を増悪させる2016

    • Author(s)
      小西博之、小林正明、高井俊行、木山博資
    • Organizer
      第59回日本神経化学会大会
    • Place of Presentation
      福岡国際会議場(福岡県福岡市)
    • Related Report
      2016 Research-status Report
  • [Presentation] TREM2/DAP12 を介する神経損傷後のミクログリア活性化2016

    • Author(s)
      小西博之、小林正明、木山博資
    • Organizer
      第6回生理学研究所・名古屋大学医学系研究科合同シンポジウム
    • Place of Presentation
      名古屋大学医学部(愛知県名古屋市)
    • Related Report
      2016 Research-status Report
  • [Presentation] TREM2/DAP12 signal in microglia exacerbates neuropathic pain2016

    • Author(s)
      小西博之、小林正明、木山博資
    • Organizer
      第21回グリア研究会
    • Place of Presentation
      千里ライフセンター(大阪府豊中市)
    • Related Report
      2016 Research-status Report
  • [Presentation] Alteration of phospholipid localization induces microglial ramification2016

    • Author(s)
      Tokizane K, Konishi H, Makide K, Kawana H, Nakamuta S, Kaibuchi K, Ohwada T, Aoki J, Kiyama H
    • Organizer
      Cold Spring Harbor Asia Conferences, New insights into Glia function & Dysfunction
    • Place of Presentation
      World Hotel Grand Dushulake Suzhou (Suzhou, China)
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research
  • [Remarks] 個人ホームページ

    • URL

      https://www.med.nagoya-u.ac.jp/anatomy2/konishi.htm

    • Related Report
      2018 Annual Research Report
  • [Remarks] 名古屋大学 大学院医学系研究科 機能組織学 ホームページ

    • URL

      https://www.med.nagoya-u.ac.jp/Anatomy2/

    • Related Report
      2017 Research-status Report
  • [Remarks] 名古屋大学大学院医学系研究科 機能組織学 ホームページ

    • URL

      https://www.med.nagoya-u.ac.jp/Anatomy2/

    • Related Report
      2016 Research-status Report

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

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