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Effect of brain erythropoietin on neuron and glia in the hypoxic and ischemic damage of neonatal brain

Research Project

Project/Area Number 25461651
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Embryonic/Neonatal medicine
Research InstitutionNagoya City University

Principal Investigator

Aoyama Mineyoshi  名古屋市立大学, 薬学研究科(研究院), 教授 (70363918)

Co-Investigator(Kenkyū-buntansha) ASAI KIYOFUMI  名古屋市立大学, 大学院医学研究科, 教授 (70212462)
Project Period (FY) 2013-04-01 – 2016-03-31
Project Status Completed (Fiscal Year 2015)
Budget Amount *help
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2014: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2013: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Keywordsエリスロポエチン / ミクログリア / 神経保護 / 細胞活性 / グリア / ニューロン / 細胞分化 / ヒトiPS細胞
Outline of Final Research Achievements

Recently, it has been demonstrated that erythropoietin (EPO), a hematopoietic hormone, has a neuroprotective effect and EPO receptor (EPOR) is expressed in the central nervous system (CNS). In our previous study, brain immune cells microglia had higher expressions of EPOR than astrocytes and neurons. In vitro , we assessed the effect of EPO using microglial cell line BV-2 activated by lipopolysaccharide(LPS). LPS increased the gene expressions of cytokines in BV-2, but these increases were significantly suppressed by EPO. Next, LPS treatment increased the phagocytosis in BV-2 compared with untreated BV-2, but this increase was significantly suppressed by EPO. In vivo, LPS induced microglia to be activated types, but EPO alleviated the active morphological change. These data indicated that LPS made microglia activated and cytotoxic, but EPO-EPOR signal might attenuate LPS-induced microglial cytotoxic activation.

Report

(4 results)
  • 2015 Annual Research Report   Final Research Report ( PDF )
  • 2014 Research-status Report
  • 2013 Research-status Report
  • Research Products

    (23 results)

All 2016 2015 2014 2013

All Journal Article (4 results) (of which Peer Reviewed: 4 results,  Acknowledgement Compliant: 2 results) Presentation (19 results) (of which Int'l Joint Research: 3 results)

  • [Journal Article] Oncolytic reovirus combined with trastuzumab enhances antitumor efficacy through TRAIL signaling in human HER2-positive gastric cancer cells2015

    • Author(s)
      Hamano S., Mori Y., Aoyama M., Kataoka H., Tanaka M., Ebi M., Kubota E., Mizoshita T., Tanida S., Johnston R.N., Asai K., Joh T.
    • Journal Title

      Cancer Lett

      Volume: 356(2 Pt B) Issue: 2 Pages: 846-854

    • DOI

      10.1016/j.canlet.2014.10.046

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Inflammatory cytokine tumor necrosis factor α suppresses neuroprotective endogenous erythropoietin from astrocytes mediated by hypoxia-inducible factor-2α2014

    • Author(s)
      Nagaya Y., Aoyama M., Tamura T., Kakita H., Kato S., Hida H., Saitoh S., Asai K.
    • Journal Title

      Eur J Neurosci

      Volume: 40(11) Issue: 11 Pages: 3620-3626

    • DOI

      10.1111/ejn.12747

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Prognostic impact of miR-145 down-regulation in adult T-cell leukemia/ lymphoma2014

    • Author(s)
      Hongjing Xia, Seiji Yamada, Mineyoshi Aoyama, Fumihiko Sato, Ayako Masaki, Yan Ge, Masaki Ri, Takashi Ishida, Ryuzo Ueda, Atae Utsunomiya, Kiyofumi Asai, Hiroshi Inagaki
    • Journal Title

      Human pathology

      Volume: S0046-8177(14) Issue: 6 Pages: 53-57

    • DOI

      10.1016/j.humpath.2014.01.017

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Tumor necrosis factor stimulates osteoclastogenesis from human bone marrow cells under hypoxic conditions.2014

    • Author(s)
      Nomura T, Aoyama M, Waguri-Nagaya Y, Goto Y, Suzuki M, Miyazawa K, Asai K, Goto S.
    • Journal Title

      Exp Cell Res

      Volume: 321 Issue: 2 Pages: 167-177

    • DOI

      10.1016/j.yexcr.2013.11.020

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Presentation] Neuroprotective erythropoietin (EPO) from astrocyte was suppressed by inflammatory cytokine tumor necrosis factor α (TNFα)2016

    • Author(s)
      Aoyama M, Nagoya Y, Asai K
    • Organizer
      第89回日本薬理学会年会
    • Place of Presentation
      パシフィコ横浜(横浜)
    • Year and Date
      2016-03-09
    • Related Report
      2015 Annual Research Report
  • [Presentation] 低酸素負荷による微小環境の変化は、TNFα刺激で誘導されるヒト骨髄細胞由来破骨細胞形成を促進する2015

    • Author(s)
      後藤洋、 野村隆之、 青山峰芳、 関谷健夫、 永谷祐子、 宮澤健、 浅井清文、 後藤滋巳
    • Organizer
      第74回日本矯正歯科学会大会
    • Place of Presentation
      福岡国際会議場(福岡)
    • Year and Date
      2015-11-18
    • Related Report
      2015 Annual Research Report
  • [Presentation] Erythropoietin Attenuated the Microglial Cytotoxity2015

    • Author(s)
      Tamura T, Aoyama M, Kakita H, Ukai S, Asai K, Sobue K
    • Organizer
      Neuroscience 2015, the Society for Neuroscience Annual Meeting 2015
    • Place of Presentation
      Chicago, IL, USA
    • Year and Date
      2015-10-17
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research
  • [Presentation] The inhibitory effect of synthetic disease-modifing anti-rheumatic drugs and steroids on gliostain/platelet-derived endothelial cell growth factor production in human fibroblast-like synoviocytes2015

    • Author(s)
      Kawaguchi Y, Waguri-Nagaya Y, Ikuta K, Tatematsu N, Kobayashi M, Goto H, Nozaki M, Aoyama M, Asai K, Otsuka T
    • Organizer
      European League Against Rheumatism 2015
    • Place of Presentation
      Roma, Italy
    • Year and Date
      2015-06-10
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research
  • [Presentation] A role for p38 mitogen-activated protein kinase (MAPK) in gliostain production in rheumatoid fibroblast-like synoviocytes2015

    • Author(s)
      Ikuta K, Waguri-Nagaya Y, Tatematsu N, Kawaguchi Y, Terazawa T, Kobayashi M, Aoyama M, Asai K, Otsuka T
    • Organizer
      European League Against Rheumatism 2015
    • Place of Presentation
      Roma, Italy
    • Year and Date
      2015-06-10
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research
  • [Presentation] インフルエンザウイルス脳症においてジクロフェナックナトリウムがミクログリアの機能に与える影響2015

    • Author(s)
      青山峰芳、垣田博樹、浅井清文
    • Organizer
      第88回日本薬理学会年会
    • Place of Presentation
      名古屋国際会議場(名古屋)
    • Year and Date
      2015-03-18 – 2015-03-20
    • Related Report
      2014 Research-status Report
  • [Presentation] 炎症性サイトカインTNFαによるアストロサイトから分泌される神経保護因子エリスロポエチンの産生抑制メカニズムの解明2014

    • Author(s)
      青山峰芳、長屋嘉顕、垣田博樹、田村哲也、浅井清文
    • Organizer
      第19回グリア研究会
    • Place of Presentation
      東京商工会議所(東京)
    • Year and Date
      2014-12-06
    • Related Report
      2014 Research-status Report
  • [Presentation] Astrocyte-derived erythropoietin protects the oligodendrocyte precursor cell against hypoxic and reoxygenation injury.2014

    • Author(s)
      Aoyama M, Kato S, Kakita H, Hida H, Sawamoto K, Asai K.
    • Organizer
      Neuroscience 2014, the Society for Neuroscience Annual Meeting 2014
    • Place of Presentation
      Washington, DC, U.S.A.
    • Year and Date
      2014-11-15 – 2014-11-19
    • Related Report
      2014 Research-status Report
  • [Presentation] The hypoxic induction of endogenous erythropoietin (EPO) from astrocyte was suppressed by inflammatory cytokine tumor necrosis factor (TNF).2014

    • Author(s)
      Tamura T., Nagaya Y., Aoyama M., Kakita H., Kato S., Hida H., Asai K.
    • Organizer
      Neuroscience 2014, the Society for Neuroscience Annual Meeting 2014
    • Place of Presentation
      Washington, DC, U.S.A.
    • Year and Date
      2014-11-15 – 2014-11-19
    • Related Report
      2014 Research-status Report
  • [Presentation] ジクロフェナックがアストロサイトとミクログリアのiNOS/NOx産生および活性化に及ぼす影響2014

    • Author(s)
      垣田博樹、青山峰芳、浅井清文
    • Organizer
      第61回中部日本生理学会
    • Place of Presentation
      名古屋市立大学(名古屋)
    • Year and Date
      2014-11-07 – 2014-11-08
    • Related Report
      2014 Research-status Report
  • [Presentation] 炎症性サイトカインTNFによるアストロサイト由来エリスロポエチン発現の抑制2014

    • Author(s)
      青山峰芳、長屋嘉顕、田村哲也、垣田博樹、加藤晋、飛田秀樹、浅井清文
    • Organizer
      第57回日本神経化学会大会
    • Place of Presentation
      奈良県文化会館、奈良県新公会堂(奈良)
    • Year and Date
      2014-09-29 – 2014-10-01
    • Related Report
      2014 Research-status Report
  • [Presentation] Enhanced antitumor effects of oncolytic reovirus and trastuzumab combination therapy in human HER2-positive gastric cancer.2014

    • Author(s)
      Kataoka H., Hamano S., Aoyama M., Mori Y., Tanaka M., Hayashi N., Kubota E., Johnston R., Joh T.
    • Organizer
      23rd Biennial Congress of the European association for cancer research 2014
    • Place of Presentation
      Munich, Germany
    • Year and Date
      2014-07-05 – 2014-07-08
    • Related Report
      2014 Research-status Report
  • [Presentation] The importance of gliostatin as an indicator of disease activity in patients with rheumatoid arthritis.2014

    • Author(s)
      Ikuta K., Waguri-Nagaya Y., Tatematsu N., Kawaguchi Y., Kobayashi. M., Aoyama M., Asai K., Otsuka T.
    • Organizer
      European League Against Rheunatism 2014
    • Place of Presentation
      Paris, France
    • Year and Date
      2014-06-11 – 2014-06-14
    • Related Report
      2014 Research-status Report
  • [Presentation] Gliostatin regulates vascular endothelial growth-factor production in human fibroblast-like synoviocytes.2014

    • Author(s)
      Kawaguchi Y., Waguri-Nagaya Y., Tatematsu N., Kobayashi M., Goto H., Nozaki M., Ikuta K., Aoyama M., Asai K., Otsuka T.
    • Organizer
      European League Against Rheunatism 2014
    • Place of Presentation
      Paris, France
    • Year and Date
      2014-06-11 – 2014-06-14
    • Related Report
      2014 Research-status Report
  • [Presentation] Erythropoietin released from astrocyte protects oligodendrocyte precursor cell damage against hypoxic and reoxygenation injury2014

    • Author(s)
      Mineyoshi Aoyama, Shin Kato, Yoshiaki Nagaya, Tetsuya Tamura, Hiroki Kakita, Hideki Hida, Kiyofumi Asai
    • Organizer
      第91回日本生理学会大会
    • Place of Presentation
      鹿児島大学(鹿児島)
    • Related Report
      2013 Research-status Report
  • [Presentation] エリスロポエチン(EPO)による脳保護効果の発現機序解明2014

    • Author(s)
      田村哲也、青山峰芳、小宮良輔、冨田麻衣子、藤掛数馬、吉澤佐也、 播磨恵、 太田晴子、藤田義人、祖父江和哉
    • Organizer
      第41回日本集中治療学会学術集会
    • Place of Presentation
      国立京都国際会館(京都)
    • Related Report
      2013 Research-status Report
  • [Presentation] 培養アストロサイトでのエリスロポエチン発現における炎症性サイトカインTNF-αの効果2014

    • Author(s)
      長屋嘉顕、田村哲也、青山峰芳、浅井清文
    • Organizer
      第18回グリア研究会
    • Place of Presentation
      仙台国際センター(仙台)
    • Related Report
      2013 Research-status Report
  • [Presentation] アストロサイト由来エリスロポエチンによるオリゴデンドロサイト前駆細胞への細胞障害抑制効果2013

    • Author(s)
      青山峰芳、加藤晋、垣田博樹、飛田秀樹、浅井清文
    • Organizer
      第60回中部日本生理学会
    • Place of Presentation
      岐阜大学(岐阜)
    • Related Report
      2013 Research-status Report
  • [Presentation] Diclofenac enhances proinflammatory cytokine-induced phagocytosis of cultured microglia via nitric oxide production2013

    • Author(s)
      Mineyoshi Aoyama, Hiroki Kakita, Yoshiaki Nagaya, Mieko Suzuki, Kiyofumi Asai
    • Organizer
      Neuro2013
    • Place of Presentation
      国立京都国際会館(京都)
    • Related Report
      2013 Research-status Report

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Published: 2014-07-25   Modified: 2019-07-29  

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