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Role of functional change of microglia in neuropathogenesis of prion diseases

Research Project

Project/Area Number 23248050
Research Category

Grant-in-Aid for Scientific Research (A)

Allocation TypeSingle-year Grants
Section一般
Research Field Applied veterinary science
Research InstitutionHokkaido University

Principal Investigator

HORIUCHI Motohiro  北海道大学, (連合)獣医学研究科, 教授 (30219216)

Co-Investigator(Kenkyū-buntansha) INANAMI Osamu  北海道大学, 大学院獣医学研究科, 教授 (10193559)
HASEBE Rie  北海道大学, 大学院獣医学研究科, 講師 (70431335)
SASSA Yukiko  北海道大学, 大学院獣医学研究科, 博士研究員 (20582464)
Co-Investigator(Renkei-kenkyūsha) OHSIMA Masanobu  金沢大学, がん研究所, 教授 (40324610)
Project Period (FY) 2011-04-01 – 2015-03-31
Project Status Completed (Fiscal Year 2014)
Budget Amount *help
¥47,320,000 (Direct Cost: ¥36,400,000、Indirect Cost: ¥10,920,000)
Fiscal Year 2014: ¥9,360,000 (Direct Cost: ¥7,200,000、Indirect Cost: ¥2,160,000)
Fiscal Year 2013: ¥10,140,000 (Direct Cost: ¥7,800,000、Indirect Cost: ¥2,340,000)
Fiscal Year 2012: ¥11,180,000 (Direct Cost: ¥8,600,000、Indirect Cost: ¥2,580,000)
Fiscal Year 2011: ¥16,640,000 (Direct Cost: ¥12,800,000、Indirect Cost: ¥3,840,000)
Keywordsプリオン病 / ミクログリア / 自然免疫 / アストロサイト / 抗炎症性サイトカイン / 磁気細胞分離法 / IL10 / CD14 / プリオン / 次世代シークエンサー / 網羅的遺伝子発現解析 / CCL2 / CXCL10 / IL-10 / IL-17 / サイトカイン
Outline of Final Research Achievements

We established PrPSc-specific staining method and using this method we elucidated a part of neuropathophysiology in the early stage of prion infection; astrocytes recognize prion propagation directly or subtle changes in neurons by prion propagation and astrocyte activation precedes over microglial activation.
Gene expression analysis of microglia in prion-infected mice showed that microglia play a neuroprotective role by secreting neurotrophic factors at the early stage of prion infection in the early stage of prion infection, but the microglial activation state shifts to pro-inflammatory or neurotoxic state along with the progression of prion disease. Furthermore, anti-inflammatory cytokines such as IL-10 interfere the propagation of prions in brain.

Report

(5 results)
  • 2014 Annual Research Report   Final Research Report ( PDF )
  • 2013 Annual Research Report
  • 2012 Annual Research Report
  • 2011 Annual Research Report
  • Research Products

    (35 results)

All 2014 2013 2012 2011

All Journal Article (13 results) (of which Peer Reviewed: 11 results,  Open Access: 4 results,  Acknowledgement Compliant: 2 results) Presentation (20 results) (of which Invited: 2 results) Book (2 results)

  • [Journal Article] Characterization of intracellular dynamics of inoculated PrP-res and newly generated PrP(Sc) during early stage prion infection in Neuro2a cells.2014

    • Author(s)
      Yamasaki T, Baron GS, Suzuki A, Hasebe R, Horiuchi M.
    • Journal Title

      Virology

      Volume: 451-451 Pages: 324-325

    • DOI

      10.1016/j.virol.2013.11.007

    • NAID

      120005425355

    • Related Report
      2014 Annual Research Report 2013 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Genetic diversity in the prion protein gene (PRNP) of domestic cattle and water buffaloes in Vietnam, Indonesia and Thailand.2014

    • Author(s)
      Uchida L, Heriyanto A, Thongchai C, Hanh TT, Horiuchi M, Ishihara K, Tamura Y, Muramatsu Y
    • Journal Title

      J Vet Med Sci

      Volume: 76 Pages: 1001-1008

    • NAID

      130003391317

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Comparison of the anti-prion mechanism of four different anti-prion compounds, anti-PrP monoclonal antibody 44B1, pentosan polysulfate, chlorpromazine, and U18666A, in prion-infected mouse neuroblastoma cells.2014

    • Author(s)
      Yamasaki T, Suzuki A, Hasebe R, Horiuchi M
    • Journal Title

      PLoS One

      Volume: 9 Issue: 9 Pages: e106516-e106516

    • DOI

      10.1371/journal.pone.0106516

    • NAID

      120005476205

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Temporary upregulation of anti-inflammatory cytokine IL-13 expression in the brains of CD14 deficient mice in the early stage of prion infection.2014

    • Author(s)
      Hasebe R, Suzuki A, Yamasaki T, Horiuchi M
    • Journal Title

      Biochem Biophys Res Commun

      Volume: 454 Issue: 1 Pages: 125-130

    • DOI

      10.1016/j.bbrc.2014.10.043

    • NAID

      120005540293

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Therapeutic effect of peripheral administration of an anti-prion protein antibody on mice infected with prions.2013

    • Author(s)
      Ohsawa N, Song CH, Suzuki A, Furuoka H, Hasebe R, Horiuchi M
    • Journal Title

      Microbiology and Immunology

      Volume: 57 Issue: 4 Pages: 288-297

    • DOI

      10.1111/1348-0421.12037

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Absence of CD14 delays progression of prion diseases accompanied by increased microglial activation.2013

    • Author(s)
      Sakai K, Hasebe R, Takahashi Y, Song CH, Suzuki A, Yamasaki T, Horiuchi M.
    • Journal Title

      Journal of Virology

      Volume: 87 Issue: 24 Pages: 13433-13445

    • DOI

      10.1128/jvi.02072-13

    • NAID

      120005455879

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] プリオンの感染と細胞内動態2013

    • Author(s)
      山﨑 剛士、堀内 基広
    • Journal Title

      Dementia Japan

      Volume: 27 Pages: 215-224

    • Related Report
      2013 Annual Research Report
  • [Journal Article] Therapeutic effect of peripheral administration of an anti-prion protein antibody on mice infected with prions2013

    • Author(s)
      Ohsawa, N.
    • Journal Title

      Microbiology and Immunology

      Volume: 57 Pages: n/a-n/a

    • DOI

      10.1111/j.1348-0421.12037

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Brucella abortus exploits a cellular prion protein on intestinal M cells as an invasive receptor.2012

    • Author(s)
      Nakato G, Hase K, Suzuki M, Kimura M, Ato M, Hanazato M, Tobiume M, Horiuchi M, Atarashi R, Nishida N, Watarai M, Imaoka K, Ohno H
    • Journal Title

      Journal of Immunology

      Volume: 189(4) Issue: 4 Pages: 1540-4

    • DOI

      10.4049/jimmunol.1103332

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Alternative BSE Risk Assessment Methodology of Imported Beef and Beef Offal to Japan2012

    • Author(s)
      Yoshikawa, Y.
    • Journal Title

      Journal of Veterinary Medical Science

      Volume: 74 Pages: 959-968

    • Related Report
      2012 Annual Research Report
  • [Journal Article] Characterization of intracellular localization of PrP^<Sc> in prioninfected cells using monoclonal antibody that recognizes the region consisting of amino acids 119-127 of mouse PrP2012

    • Author(s)
      Yamasaki T., Suzuki A., Shimizu T., Watarai M., Hasebe R., Horiuchi M.
    • Journal Title

      Journal of General Virology

      Volume: vol.93 no.3 Issue: 3 Pages: 668-680

    • DOI

      10.1099/vir.0.037101-0

    • Related Report
      2012 Annual Research Report 2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Reaction of complement factors varies with prion strains in vitro and in vivo2012

    • Author(s)
      Hasebe, R.
    • Journal Title

      Virology

      Volume: 423 Issue: 2 Pages: 205-213

    • DOI

      10.1016/j.virol.2011.11.017

    • Related Report
      2012 Annual Research Report 2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Identification of chemoattractive factors involved in the migration of bone marrow-derived mesenchymal stem cells to brain lesions caused by prion2011

    • Author(s)
      Song, C.H., et al
    • Journal Title

      J.Virol.

      Volume: 85 Issue: 21 Pages: 11069-11078

    • DOI

      10.1128/jvi.05318-11

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Presentation] フローサイトメトリーによるプリオン感染細胞の検出2014

    • Author(s)
      山崎 剛士、鈴木 章夫、長谷部 理絵、堀内 基広
    • Organizer
      第59回日本ウイルス学会
    • Place of Presentation
      パシフィコ横浜、横浜
    • Year and Date
      2014-11-10
    • Related Report
      2014 Annual Research Report
  • [Presentation] igh throughput detection of PrPSc from prion-infected cells without PK-treatment: cell-based ELISA for novel screening method for anti-prion compounds2014

    • Author(s)
      Shan Z, Yamasaki T, Suzuki A, Hasebe R, Horiuchi M
    • Organizer
      Asian Pacific Prion Symposium 2014
    • Place of Presentation
      済州島国際会議場、済州、韓国
    • Year and Date
      2014-07-07 – 2014-07-08
    • Related Report
      2014 Annual Research Report
  • [Presentation] Involvement of CD14 in neuropathogenesis of prion diseases2014

    • Author(s)
      Hasebe R, Sakai K, Song C-H, Takahashi Y, Suzuki A, Yamasaki T, Horiuchi M
    • Organizer
      Asian Pacific Prion Symposium 2014
    • Place of Presentation
      済州島国際会議場、済州、韓国
    • Year and Date
      2014-07-07
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] Comparison of the anti-prion mechanism of four different anti-prion compounds, anti-PrP monoclonal antibody 44B1, pentosan polysulfate, chlorpromazine, and U18666A, in prion-infected mouse neuroblastoma cells2014

    • Author(s)
      Yamasaki T, Suzuki A, Hasebe R, Horiuchi M
    • Organizer
      Asian Pacific Prion Symposium 2014
    • Place of Presentation
      済州島国際会議場、済州、韓国
    • Year and Date
      2014-07-07
    • Related Report
      2014 Annual Research Report
  • [Presentation] Analysis of prion infection in primary cortical neurons2014

    • Author(s)
      Fujiwara A, Sassa Y, Yamasaki T, Hasebe R, Horiuchi M
    • Organizer
      Prion2014
    • Place of Presentation
      先端国際大学、トリエステ、イタリア
    • Year and Date
      2014-05-27 – 2014-05-29
    • Related Report
      2014 Annual Research Report
  • [Presentation] Analysis of mechanism for PrPSc-specific detection by anti-PrP monoclonal antibody mAb1322014

    • Author(s)
      Suzuki A, Yamasaki T, Hasebe R, Horiuchi M
    • Organizer
      Prion2014
    • Place of Presentation
      先端国際大学、トリエステ、イタリア
    • Year and Date
      2014-05-27 – 2014-05-29
    • Related Report
      2014 Annual Research Report
  • [Presentation] Analysis of microglial activation state in brains of prion-infected mice.2013

    • Author(s)
      Horiuchi, M., Kabuki, H., and Hasebe, R.
    • Organizer
      Prion 2013
    • Place of Presentation
      Banff, (Fair montanff Spring Hotel) Canada
    • Related Report
      2013 Annual Research Report
  • [Presentation] Reaction of complement factors on scrapie-infected primary-cultured neurons temporarily increases permeability of plasma membrane.2013

    • Author(s)
      Hasebe, R., Suzuki A., Yamasaki, T., and Horiuchi, M.
    • Organizer
      Prion 2013
    • Place of Presentation
      Banff, Fair montanff Spring Hotel (Canada)
    • Related Report
      2013 Annual Research Report
  • [Presentation] Analysis of microglial activation state in brains of prion-infected mice.2013

    • Author(s)
      Kabuki, H., Yamasaki, T., Hasebe, R., and Horiuchi, M.
    • Organizer
      Asia Pacific Prion Symposium 2013
    • Place of Presentation
      Sasebo, Huis Ten Bosch (Japan)
    • Related Report
      2013 Annual Research Report
  • [Presentation] Absence of CD14 delays progression of prion diseases accompanied by increased microglial activation.2013

    • Author(s)
      4) Sakai, K., Hasebe, R., Takahashi, Y., Song, C.-H., Suzuki, A., Yamasaki, T., Horiuchi, M.
    • Organizer
      Expanding Prion Horizon 2013
    • Place of Presentation
      Fort Collins, Colorado State University (USA)
    • Related Report
      2013 Annual Research Report
  • [Presentation] Analysis of PrPSc accumulation and glial cell activation in brains of prion-infected mice at the early stage of infection2012

    • Author(s)
      Horiuchi, M.
    • Organizer
      Prion2012
    • Place of Presentation
      VU University, Amsterdam, The Netherland
    • Related Report
      2012 Annual Research Report
  • [Presentation] A decreased expression of pre-synaptic markers in neurons in differentiated neurospheres infected with BSE-derived prion strain2012

    • Author(s)
      Sassa, Y.
    • Organizer
      Prion2012
    • Place of Presentation
      VU University, Amsterdam, The Netherland
    • Related Report
      2012 Annual Research Report
  • [Presentation] Construction of mAb132-EGFP fusion proteins as a PrPSc-specific probe2012

    • Author(s)
      Suzuki, A.
    • Organizer
      Asia Pacific Prion Symposium 2012
    • Place of Presentation
      Pacifico Yokohama, Yokohama, Japan
    • Related Report
      2012 Annual Research Report
  • [Presentation] Analysis of intracellular dynamics of inoculated PrP-res and newly generated PrPSc in Neuro2a cells2012

    • Author(s)
      Yamasaki, T.
    • Organizer
      Asia Pacific Prion Symposium 2012
    • Place of Presentation
      Pacifico Yokohama, Yokohama, Japan
    • Related Report
      2012 Annual Research Report
  • [Presentation] Immuno- and cell-therapy as possible treatment for prion diseases2012

    • Author(s)
      Horiuchi, M.
    • Organizer
      BBSRC Japan Partnering Awards
    • Place of Presentation
      The Roslin Institute & Royal (Dick) School of Veterinary Sciences, Edinburgh, UK
    • Related Report
      2012 Annual Research Report
    • Invited
  • [Presentation] 異常型プリオンタンパク質の細胞内増殖2011

    • Author(s)
      堀内基広、山崎剛士
    • Organizer
      第30回日本認知症学会
    • Place of Presentation
      タワーホール船堀(東京)(招待講演)
    • Year and Date
      2011-11-11
    • Related Report
      2011 Annual Research Report
  • [Presentation] Detection of newly generataed PrPSc in Neuro2a cells inoculated with fluorescent-dye labeled purified PrPSc2011

    • Author(s)
      Yamasaki T, et al.
    • Organizer
      XV International Congress of Virology
    • Place of Presentation
      Sapporo Convention Center (Japan)
    • Year and Date
      2011-09-11
    • Related Report
      2011 Annual Research Report
  • [Presentation] Involvement of CD14 in the early neuropathogenesis of prion disease2011

    • Author(s)
      Hasebe R, et al.
    • Organizer
      XV International Congress of Virology
    • Place of Presentation
      Sapporo Convention Center (Japan)
    • Year and Date
      2011-09-11
    • Related Report
      2011 Annual Research Report
  • [Presentation] Involvement of the endosomal Cl-/H+ antiporter Clc-5 in the formation of PrP-res in prion-infected Neuro2a mouse neuroblastoma cells2011

    • Author(s)
      Nakamitsu S, et al.
    • Organizer
      APPS2011
    • Place of Presentation
      Hotel Marroad Karuizawa (Japan)
    • Year and Date
      2011-07-10
    • Related Report
      2011 Annual Research Report
  • [Presentation] Characterization of prion infection in differentiated mouse neurospheres2011

    • Author(s)
      Sassa Y, et al.
    • Organizer
      Prion2011
    • Place of Presentation
      Fairmont Queen Elizabeth (Canada)
    • Year and Date
      2011-05-17
    • Related Report
      2011 Annual Research Report
  • [Book] 最新医学「プリオン」2011

    • Author(s)
      堀内基広
    • Total Pages
      8
    • Publisher
      最新医学社
    • Related Report
      2011 Annual Research Report
  • [Book] 獣医微生物学(第3版)「プリオンとプリオン病」2011

    • Author(s)
      堀内基広
    • Total Pages
      6
    • Publisher
      文永堂出版
    • Related Report
      2011 Annual Research Report

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Published: 2011-04-06   Modified: 2019-07-29  

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