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脳組織サイトカイン環境の加齢に伴う炎症性変化を誘導する髄膜・脈絡叢の免疫系構築

Research Project

Project/Area Number 12J40278
Research Category

Grant-in-Aid for JSPS Fellows

Allocation TypeSingle-year Grants
Section国内
Research Field Nerve anatomy/Neuropathology
Research InstitutionInstitute for Developmental Research, Aichi Human Service Center

Principal Investigator

石井 さなえ  愛知県心身障害者コロニー発達障害研究所, 病理学部, 特別研究員(RPD)

Project Period (FY) 2012-04-01 – 2015-03-31
Project Status Completed (Fiscal Year 2014)
Budget Amount *help
¥3,960,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥360,000)
Fiscal Year 2014: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2013: ¥1,200,000 (Direct Cost: ¥1,200,000)
Fiscal Year 2012: ¥1,200,000 (Direct Cost: ¥1,200,000)
Keywordsサイトカイン / 髄膜 / 脈絡叢 / 老化 / 炎症 / 髄膜・脈絡叢 / 加齢 / LPS / 海馬 / MultiPlex / 髄膜免疫系 / 骨髄内骨髄移植 / インターフェイス
Outline of Annual Research Achievements

本年度は以下の3点の解析を行い、①を論文にまとめた。②③は論文作成中である。
①若齢、老齢のSAMP10マウスと同月齢のB6マウスの間脳における10種類のサイトカインをLuminex MultiPlexアッセイにより一斉定量した。その結果、老齢SAMP10マウスの間脳にはCCL11, CXCL1, CXCL10, G-CSF, IL-6が同月齢のB6マウスに比べて有意に高濃度であり、免疫染色の結果、脈絡叢付着領域のアストロサイト、脳室周囲のアストロサイト及びタニサイトが強発現することがわかった。
②LPS(3mg/kg)を腹腔内投与した1, 4, 24時間後に脾臓と海馬を回収し、Luminex MultiPlexアッセイにより15種類のサイトカインを一斉定量した。その結果、LPS投与後に海馬では10種類のサイトカインが増加した。免疫染色の結果、LPS投与4時間後に増加するサイトカインは、脈絡叢及び髄膜の細胞、血管内皮細胞が発現し、その受容体は脳表や血管周囲のアストロサイトの終足に発現した。LPS投与24時間後に増加するサイトカインはアストロサイトが発現した。
③7日, 4週齢, 2, 8, 13, 20カ月齢のSAMP10マウス、コントロールマウス(SAMR1マウス、B6マウス)を用いて、海馬における10種類のサイトカイン濃度をLuminex MultiPlexアッセイにて定量した。その結果、加齢により増加するのはCXCL10のみで、B6マウスやSAMR1マウスに比べてSAMP10マウスでは早期に増加した。

Research Progress Status

26年度が最終年度であるため、記入しない。

Strategy for Future Research Activity

26年度が最終年度であるため、記入しない。

Report

(3 results)
  • 2014 Annual Research Report
  • 2013 Annual Research Report
  • 2012 Annual Research Report
  • Research Products

    (24 results)

All 2015 2014 2013 2012

All Journal Article (11 results) (of which Peer Reviewed: 11 results,  Acknowledgement Compliant: 4 results,  Open Access: 1 results) Presentation (12 results) (of which Invited: 2 results) Book (1 results)

  • [Journal Article] Increased recruitment of bone marrow-derived cells into the brain associated with altered brain cytokine profile in senescence-accelerated mice2015

    • Author(s)
      Hasegawa-Ishii S., Inaba M., Ming Li., Ming S., Umegaki H., Ikehara S. and Shimada A.
    • Journal Title

      Brain Struct. Funct.

      Volume: in press

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Dynamics of bone marrow-derived cells relevant to the brain-immune cell-cell interactions under non-inflammatory conditions.2014

    • Author(s)
      Hasegawa-Ishii S., Inaba M., Li Ming., Umegaki H., Ikehara S. and Shimada A.
    • Journal Title

      Curr. Trends Neurol.

      Volume: 8 Pages: 39-52

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Novel flame-shift mutation in Slc5a2 encoding SGLT2 in a strain of senescence-accelerated mouse SAMP10.2014

    • Author(s)
      Unno K., Yamamoto H., Toda M., Hagiwara S., Iguchi K., Hoshino M., Takabayashi F., Hasegawa-Ishii S., Shimada A., Hosokawa M., Higuchi K and Mori M.
    • Journal Title

      Biochem. Biophys. Res. Commun.

      Volume: 454 Issue: 1 Pages: 89-94

    • DOI

      10.1016/j.bbrc.2014.10.039

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] 知的障害および発達障害の病態形成に関与する脳と免疫系の相互作用.2014

    • Author(s)
      島田厚良、石井さなえ.
    • Journal Title

      中部大学現代教育学部紀要

      Volume: 7 Pages: 21-25

    • NAID

      40020371354

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Niemann-Pick disease type Cl predominantly involving the front otemporal region, with cortical and brainstem Lewy bodies : An autopsy case.2014

    • Author(s)
      Chiba Y., Komori H., Takei S., Hasegawa-Ishii S., Kawamura N., Adachi K., Nanba E., Hosokawa M., Enokido Y., Kouchi Z., Yoshida F., Shimada A.
    • Journal Title

      Neuropathology :

      Volume: 34(1) Issue: 1 Pages: 49-57

    • DOI

      10.1111/neup.12047

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Excitotoxicity-induced immediate surge in hippocampal prostanoid production has latent effects that promote chronic progressive neuronal death.2013

    • Author(s)
      Yoshikawa K., Kita Y., Furukawa A., Kawamura N., Hasegawa-Ishii S., Chiba Y., Takei S., Maruyama K., Shimizu T., Shimada A.
    • Journal Title

      Prostaglandins Leukot Essent Fatty Acids.

      Volume: 88(5) Issue: 5 Pages: 373-381

    • DOI

      10.1016/j.plefa.2013.02.007

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Exome sequencing of senescence-accelerated mice (SAM) reveals deleterious mutations in degenerative disease-causing genes.2013

    • Author(s)
      Tanisawa K., Mikami E., Fuku N., Honda Y., Honda S., Ohsawa I., Ito M., Endo S., Ihara K., Ohno K., Kishimoto Y., Ishigami A., Maruyama N., Sawabe M., Iseki H., Okazaki Y., Hasegawa-Ishii S., Takei S., Shimada A., Hosokawa M., Mori M., Higuchi K., Takeda T., Higuchi M., Tanaka M.
    • Journal Title

      BMC Genomics.

      Volume: 14(1): Issue: 1 Pages: 248-248

    • DOI

      10.1186/1471-2164-14-248

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Immunohistochemical localization of aggresomal proteins in glial cytoplasmic inclusions in multiple system atrophy.2012

    • Author(s)
      Chiba Y., Takei S., Kawamura N., Kawaguchi Y., Sasaki K., Hasegawa-Ishii S., Furukawa A., Hosokawa M., Shimada A.
    • Journal Title

      Neuropathol. Appl. Neurobiol.

      Volume: 38(6) Issue: 6 Pages: 559-71

    • DOI

      10.1111/j.1365-2990.2011.01229.x

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Immunohistochemical demonstration of increased prostaglandin F(2α) levels in the rat hippocampus following kainic acid-induced seizures.2012

    • Author(s)
      Takei S., Hasegawa-lshii S., Uekawa A., Chiba Y., Umegaki H., Hosokawa M., Woodward DF., Watanabe K., Shimada A.
    • Journal Title

      Neuroscience.

      Volume: 218 Pages: 295-304

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Selective localization of bone marrow-derived ramified cells in the brain adjacent to the attachments of choroid plexus.2012

    • Author(s)
      Hasegawa-Ishii S, Shimada A, Inaba M, Li M, Shi M, Kawamura N, Takei S, Chiba Y, Hosokawa M, Ikehara S.
    • Journal Title

      Brain Behav Immun.

      Volume: 29 Pages: 82-97

    • DOI

      10.1016/j.bbi.2012.12.010

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] 脳と免疫系の相互作用という観点から老化促進モデルマウスをとらえる2012

    • Author(s)
      島田厚良、石井さなえ
    • Journal Title

      基礎老化研究

      Volume: 36(1) Pages: 13-20

    • NAID

      10030253433

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Presentation] Brain cytokine change associated with enhanced bone marrow cell recruitment to the brain in SAM mice.2014

    • Author(s)
      HASEGAWA-ISHII, S., IKEHARA, S., INABA, M., LI, M., SHI, M., SHIMADA, A.
    • Organizer
      第37回日本基礎老化学会
    • Place of Presentation
      名古屋
    • Year and Date
      2014-06-26 – 2014-06-27
    • Related Report
      2014 Annual Research Report
  • [Presentation] Proinflammatory cytokine milieu of the brain precedes age-related neurodegeneration in SAMP10 mice.2014

    • Author(s)
      SHIMADA, A., HASEGAWA-ISHII, S., INABA, M.
    • Organizer
      第37回日本基礎老化学会
    • Place of Presentation
      名古屋
    • Year and Date
      2014-06-26 – 2014-06-27
    • Related Report
      2014 Annual Research Report
  • [Presentation] 末梢の炎症に応答する脳内サイトカイン受容・産生機構の組織細胞基盤2014

    • Author(s)
      石井さなえ、稲葉宗夫、武井史郎、島田厚良
    • Organizer
      第55回日本神経病理学会
    • Place of Presentation
      東京
    • Year and Date
      2014-06-05 – 2014-06-07
    • Related Report
      2014 Annual Research Report
  • [Presentation] Changes in profiles of brain cytokines associated with enhanced recruitment of bone marrow-derived cells into the brain in senescence-accelerated mice.2014

    • Author(s)
      Hasegawa-Ishii, S., Ikehara, S., Inaba, M., Li, M., Shi, M., Takei, S. and Shimada, A.
    • Organizer
      21st PsychoNeuroImmunology Resarch Society annual meeting
    • Place of Presentation
      ペンシルバニア
    • Year and Date
      2014-05-28 – 2014-05-31
    • Related Report
      2014 Annual Research Report
  • [Presentation] Enhanced recruitment of bone marrow-derived cells into the brain parenchyma in senescence-accelerated mice.2014

    • Author(s)
      Hasegawa-Ishii, S.
    • Organizer
      Neural & Behavioral Sciences Seminar Series
    • Place of Presentation
      米ペンシルバニア州立大学
    • Year and Date
      2014-05-27
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] Enhanced recruitment of bone marrow-derived cells into the brain parenchyma in senescence-accelerated mice2013

    • Author(s)
      Sanae Hasegawa-Ishii, Atsuyoshi Shimada
    • Organizer
      3rd Asia Association of Aging Research
    • Place of Presentation
      International Conference center, University of Seoul(ソウル、韓国)
    • Year and Date
      2013-11-09
    • Related Report
      2013 Annual Research Report
    • Invited
  • [Presentation] Selective localization of bone marrow-derived ramified cells in the brain adjacent to the attachments of choroid plexus*Trainee Awardを受賞。2013

    • Author(s)
      Sanae Hasegawa-Ishii, Atsuyoshi Shimada, Muneo Inaba, Ming Li, Ming Shi, Shiro Takei and Susumu Ikehara
    • Organizer
      20^<th> Annual Meeting of The PsychoNeurolm munology Research Society
    • Place of Presentation
      Radisson Blu Royal Park Hotel(ストックホルム、スウェーデン)
    • Year and Date
      2013-06-08
    • Related Report
      2013 Annual Research Report
  • [Presentation] 脳と免疫系の接点としての脈絡叢間質および付着部における細胞動態とサイトカイン発現2013

    • Author(s)
      石井さなえ、島田厚良、稲葉宗夫、李銘、石明、河村則子、武井史郎、千葉陽一、細川昌則、池原進
    • Organizer
      第54回日本神経病理学会
    • Place of Presentation
      タワーホール船堀(東京)
    • Year and Date
      2013-04-25
    • Related Report
      2013 Annual Research Report
  • [Presentation] 骨髄由来免疫系細胞が健常脳に進入する新たな経路:骨髄内骨髄移植による組織学的同定。2012

    • Author(s)
      石井さなえ、島田厚良、稲葉宗夫、李銘、石明、河村則子、武井史郎、千葉陽一、榎戸靖、河内全、細川昌則、池原進
    • Organizer
      第53回日本神経病理学会
    • Place of Presentation
      朱鷺メッセ(新潟)
    • Year and Date
      2012-06-30
    • Related Report
      2012 Annual Research Report
  • [Presentation] 老化促進モデルマウスにみられる骨髄由来細胞の脳実質へのリクルートの亢進。2012

    • Author(s)
      島田厚良、石井さなえ、稲葉宗夫、李銘、石明、河村則子、武井史郎、千葉陽一、榎戸靖、河内全、細川昌則、池原進
    • Organizer
      第53回日本神経病理学会
    • Place of Presentation
      朱鷺メッセ(新潟)
    • Year and Date
      2012-06-30
    • Related Report
      2012 Annual Research Report
  • [Presentation] Intra bone marrow procedure facilitates entry of transplanted bone marrow cells through the tenia of choroid plexus into brain parenchyma.2012

    • Author(s)
      Sanae Hasegawa-lshii, Atsuyoshi Shimada, Muneo Inaba, Ming Li, Ming Shi, Noriko Kawamura, Shiro Takei, Susumu Ikehara
    • Organizer
      19^<th> Annual Meeting of The PsychoNeurolmmunology Research Society
    • Place of Presentation
      Grand Hyatt Hotel (San Diego)
    • Year and Date
      2012-06-07
    • Related Report
      2012 Annual Research Report
  • [Presentation] Enhanced recruitment of bone marrow-derived cells into the brain parenchyma in senescence-accelerated mice.2012

    • Author(s)
      Atsuyoshi Shimada, Sanae Hasegawa-Ishii, Muneo Inaba, Ming Li, Ming Shi, Noriko Kawamura, Shiro Takei, Susumu Ikehara
    • Organizer
      19^<th> Annual Meeting of The PsychoNeurolmmunology Research Society
    • Place of Presentation
      Grand Hyatt Hotel (San Diego)
    • Year and Date
      2012-06-07
    • Related Report
      2012 Annual Research Report
  • [Book] The senescence-accelerated mouse (SAM) : Achievements and Future Directions. (Toshio Takeda, ed.)2013

    • Author(s)
      Shimada A., Hasegawa-Ishii S., Furukawa A.
    • Publisher
      SAMP10 strain as a model for the study of brain aging(In Press)
    • Related Report
      2012 Annual Research Report

URL: 

Published: 2013-04-25   Modified: 2024-03-26  

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