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Age-dependent differential responses of glial cells and Leptomeningeas during systemic inflammation

Research Project

Project/Area Number 19592171
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Pathobiological dentistry/Dental radiology
Research InstitutionOkinawa Institute of Science and Technology

Principal Investigator

SHINDOU Mayumi  Okinawa Institute of Science and Technology, 神経生物学ユニット, 研究員 (10444796)

Co-Investigator(Kenkyū-buntansha) NAKANISHI Hiroshi  九州大学, 大学院歯学研究院, 教授 (20155774)
TAKE Hiro  九州大学, 大学院歯学研究院, 研究員 (10420598)
Project Period (FY) 2007 – 2008
Project Status Completed (Fiscal Year 2008)
Budget Amount *help
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2008: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2007: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
Keywords病者行動 / 末梢炎症 / 脳炎症 / 髄膜 / グリア細胞 / サイトカイン / アジュバント関節炎 / 髄膜-グリア / 密着結合タンパク質 / LPS / 歯周病
Research Abstract

末梢炎症を誘発した若年ラットの大脳皮質のグリア細胞において抗炎症性サイトカインのIL-10ならびにTGF-β1の発現が認められた。一方、末梢炎症を誘発した中年ラットの大脳皮質では、炎症性サイトカインであるIL-1βの発現が髄膜に加えて脳実質内のグリア細胞にも認められた。さらに、末梢炎症を誘発した中年ラットの大脳皮質では髄膜における密着結合タンパク質であるオクルディンならびにZO-1の発現が低下しており、髄膜透過性の増大ならびに血球細胞の脳実質内への浸潤が認められた。初代培養髄膜細胞においてIL-1βならびにPGE_2は各々オクルディンならびにZO-1の発現を有意に低下させた。IL-10ならびにTGF-β1はIL-1βならびにPGE2の作用を抑制した。以上の結果、慢性の末梢炎症に対して髄膜.グリア連関は若齢ではニューロン保護的に、中年では逆にニューロン傷害的に作用することが明らかとなった。このことから特に中高年者では慢性の末梢炎症が深刻な脳炎症を引き起こすことが示唆された。

Report

(3 results)
  • 2008 Annual Research Report   Final Research Report ( PDF )
  • 2007 Annual Research Report
  • Research Products

    (56 results)

All 2009 2008 2007 Other

All Journal Article (20 results) (of which Peer Reviewed: 20 results) Presentation (32 results) Book (4 results)

  • [Journal Article] Age-dependent responses of glial cells and leptomeninges during systemic inflammation2008

    • Author(s)
      Wu Z., Tokuda Y., Zhang X. W., and Nakanishi H.
    • Journal Title

      Neurobiol. Disease 32

      Pages: 543-551

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] Reverse of brain aging by an overexpression of human mitochondrial transcription factor A in mice2008

    • Author(s)
      Hayashi Y., Yoshida M., Yamato M., Ide T., Wu Z., Ochi-Shindou M., Kanki T. Kang D., Sunagawa K., Tsutsui H., and Nakanishi H.
    • Journal Title

      J. Neurosci 28

      Pages: 8624-8634

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] Possible involvement of cathepsin B released by microglia in methylmercury-induced cerebellar pathological changes in the adult rats2008

    • Author(s)
      Sakamoto M., Miyamoto K. I., Wu Z., and Nakanishi H
    • Journal Title

      Neurosci. Lett 442

      Pages: 292-296

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] Inhibition of NMDA-induced outward currents by interleukin-1β in hippocampal neurons2008

    • Author(s)
      Zhang R., Yamada J., Hayashi Y., Wu Z., Koyama S., Nakanishi H
    • Journal Title

      Biochem. Biophys. Res. Commun 372

      Pages: 816-820

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] Reduced synaptic acticity precedes synaptic stripping in vagal motoneurons after axotomy2008

    • Author(s)
      Yamada J., Hayashi Y., Jinno S., Wu Z., Inoue K., Kohsaka S., Nakanishi H.
    • Journal Title

      Glia 56

      Pages: 1448-1462

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] Age-dependent responses of glial cells and leptomeninges during systemic inflammation2008

    • Author(s)
      Wu Z., et al.
    • Journal Title

      Neurobiol. Disease 32

      Pages: 543-551

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Reverse of brain aging by an overexpression of human mitochondrial transcription factor A in mice2008

    • Author(s)
      Hayashi Y., et al.
    • Journal Title

      J. Neurosci. 28

      Pages: 8624-8634

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Possible involvement of cathepsin B released by microglia in methylmercury-induced cerebellar pathological changes in the adult rats2008

    • Author(s)
      Sakamoto M., et al.
    • Journal Title

      Neurosci. Lett. 442

      Pages: 292-296

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Inhibition of NMDA-induced outward currents by interleukin-1β in hippocampal neurons2008

    • Author(s)
      Zhang R., et al.
    • Journal Title

      Biochem. Biophys. Res. Commun. 372

      Pages: 816-820

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Reduced synaptic acticity precedes synaptic stripping in vagal motoneurons after axotomy2008

    • Author(s)
      Yamada J., et al.
    • Journal Title

      Glia 56

      Pages: 1448-1462

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Involvement of lysosomal storage-induced p38 MAP kinase activation in the overproduction of nitric oxide by microglia in cathepsin D-deficient mice2007

    • Author(s)
      Yamasaki R., Zhang J., Koshiishi I., Sastradipura Suniarti D.F.,Wu Z., Peters C., Schwake M., UchiyamaY., Kira J. I., Saftig P., Utsumi H., and Nakanishi H.
    • Journal Title

      Mol. Cell. Neurosci 35

      Pages: 573-584

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] Impairment of the microglial responses to the facial nerve axotomy in cathepsin S-deficient mice2007

    • Author(s)
      Hao H. P., Doh-ura K, and Nakanishi H.
    • Journal Title

      J. Neurosci. Res 85

      Pages: 2196-2206

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] Phosphatidylserine and phosphatidylcholine- containing liposomes inhibit amyloid β and interferon-γ-induced microglial activation2007

    • Author(s)
      Hashioka S., Han Y. H., Fujii S., Kato H., Monji A., Utsumi H., Sawada M., Nakanishi H., and Kanba S.
    • Journal Title

      Free Rad. Biol. Med 42

      Pages: 945-954

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] Phospholipids modulate superoxide and nitric oxide production by lipopolysaccharide and phorbol 12-myristate-13-acetate-activated microglia2007

    • Author(s)
      Hashioka S., Han Y. H., Fujii S., Kato H., Monji A., Utsumi H., Sawada M., Nakanishi H., and Kanba S.
    • Journal Title

      Neurochem. Int 50

      Pages: 499-506

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] Involvement of PGE2 released from leptomeningeal cells in increased expression of TGF-β1 in glial cells and cortical neurons during systemic inflammation2007

    • Author(s)
      Wu Z., Hayashi Y. Zhang J., and Nakanishi H.
    • Journal Title

      J. Neurosci. Res 85

      Pages: 184-192

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] Involvement of PGE_2 released from leptomeningeal cells in increased expression of TGF-β1 in glial cells and cortical neurons during systemic inflammation.2007

    • Author(s)
      Wu Z., et. al.
    • Journal Title

      Journal of Neuroscience Research 85

      Pages: 184-192

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Phospholipids modulate superoxide and nitric oxide production by lipopolysaccharide and phorbol 12-myristate-13-acetate-activated microglia.2007

    • Author(s)
      Hashioka S., et. al.
    • Journal Title

      Neurochemistry International 50

      Pages: 499-506

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Phospholipids modulate superoxide and nitric oxide production by lipopolysaccharide and phorbol 12-myristate-13-acetate-activated microglia.2007

    • Author(s)
      Hashioka S., et. al.
    • Journal Title

      Free Radical Biology and Medicine 42

      Pages: 945-954

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Impairment of the microglial responses to the facial berve axotomy in cathepsin S-deficient mice.2007

    • Author(s)
      Hao H. P., et. al.
    • Journal Title

      Journal of Neuroscience Research 85

      Pages: 2196-2206

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Involvement of lysosomal storage-induced p38 MAP kinase activation in the overproduction of nitric oxide by microglia in cathepsin D-deficient mice.2007

    • Author(s)
      Yamasaki R., et. al.
    • Journal Title

      Molecular and Cellular Neuroscience 35

      Pages: 573-584

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Presentation] Involvement of cathepsin B in the processing and secretion of interleukin-1β in chromogranin A-stimulated microgli2009

    • Author(s)
      Nakanishi H., et al
    • Organizer
      第82回日本薬理学会年会
    • Place of Presentation
      横浜
    • Year and Date
      2009-03-17
    • Related Report
      2008 Final Research Report
  • [Presentation] Age-dependent diffrential microglial and astrocytic responses through leptomeningeas during systemic inflammation2009

    • Author(s)
      Wu Z., et al.
    • Organizer
      第82回日本薬理学会年会
    • Place of Presentation
      横浜
    • Year and Date
      2009-03-17
    • Related Report
      2008 Final Research Report
  • [Presentation] Age-dependent diffrential microglial and astrocytic responses through leptomening eas during systemic inflammation2009

    • Author(s)
      Wu Z., et al.
    • Organizer
      第82回日本薬理学会年会
    • Place of Presentation
      横浜
    • Year and Date
      2009-03-17
    • Related Report
      2008 Annual Research Report
  • [Presentation] Involvement of cathepsin B in the processing and secretion of interleukin-1β in chromogranin A-stimulated microglia2009

    • Author(s)
      Nakanishi H., et al.
    • Organizer
      第82回日本薬理学会年会
    • Place of Presentation
      横浜
    • Year and Date
      2009-03-17
    • Related Report
      2008 Annual Research Report
  • [Presentation] Involvement of p38 MAPK in interleukin-1β-induced inhibition of NMDA-induced outward currents in hippocampal neurons2008

    • Author(s)
      Zhang R.
    • Organizer
      Berlin Brain Days 2008
    • Place of Presentation
      ベルリン
    • Year and Date
      2008-12-11
    • Related Report
      2008 Final Research Report
  • [Presentation] Involvement of p38 MAPK in interleukin-1b-induced inhibition of NMDA-induced outward currents in hippocampal neurons2008

    • Author(s)
      Zhang R., Nakanishi H.
    • Organizer
      Berlin Brain Days 2008
    • Place of Presentation
      ベルリン
    • Year and Date
      2008-12-11
    • Related Report
      2008 Annual Research Report
  • [Presentation] ミトコンドリア転写因子Aの過剰発現によるミクログリア内レドックス制御ならびに老化に伴う脳機能低下の抑制2008

    • Author(s)
      中西 博, 他
    • Organizer
      第61回日本西南部会
    • Place of Presentation
      米子
    • Year and Date
      2008-11-28
    • Related Report
      2008 Annual Research Report 2008 Final Research Report
  • [Presentation] 末梢炎症に対する髄膜.グリア連関の反応の老化に伴う変容2008

    • Author(s)
      武 洲
    • Organizer
      第61回日本西南部会
    • Place of Presentation
      米子
    • Year and Date
      2008-11-28
    • Related Report
      2008 Final Research Report
  • [Presentation] 末梢炎症に対する髄膜-グリア連関の反応の老化に伴う変容2008

    • Author(s)
      武洲, 中西博
    • Organizer
      第61回日本西南部会
    • Place of Presentation
      米子
    • Year and Date
      2008-11-28
    • Related Report
      2008 Annual Research Report
  • [Presentation] Age-dependent differential regulation of tight junction proteins in the leptomeninges by glial cells during systemic inflammation2008

    • Author(s)
      Wu Z.,et al.
    • Organizer
      米国神経科学会議
    • Place of Presentation
      ワシントン DC
    • Year and Date
      2008-11-19
    • Related Report
      2008 Final Research Report
  • [Presentation] Overexpression of human TFAM prevents age-dependent memory impairment in mice by suppression of mitochondrial oxidative stress2008

    • Author(s)
      Hayashi Y., et al.
    • Organizer
      米国神経科学会議
    • Place of Presentation
      ワシントン DC
    • Year and Date
      2008-11-19
    • Related Report
      2008 Final Research Report
  • [Presentation] Reduced synaptic activity mediated by extracellular nucleotides precedes synaptic stripping after an axotomy2008

    • Author(s)
      Yamada J., et al.
    • Organizer
      米国神経科学会議
    • Place of Presentation
      ワシントン DC
    • Year and Date
      2008-11-19
    • Related Report
      2008 Final Research Report
  • [Presentation] Age-dependent differential regulation of tight junction proteins in the leptomeninges by glial cells during systemic inflammation.2008

    • Author(s)
      Wu Z., Nakanishi H.
    • Organizer
      米国神経科学会議
    • Place of Presentation
      ワシントンDC
    • Year and Date
      2008-11-19
    • Related Report
      2008 Annual Research Report
  • [Presentation] Overexpression of human TFAM prevents age-dependent memory impairment in mice by suppression of mitochondrial oxidative stress.2008

    • Author(s)
      Hayashi Y., et al.
    • Organizer
      米国神経科学会議
    • Place of Presentation
      ワシントンDC
    • Year and Date
      2008-11-19
    • Related Report
      2008 Annual Research Report
  • [Presentation] Reduced synaptic activity mediated by extracellular nucleotides precedes synaptic stripping after an axotomy2008

    • Author(s)
      Yamada J., et al.
    • Organizer
      米国神経科学会議
    • Place of Presentation
      ワシントンDC
    • Year and Date
      2008-11-19
    • Related Report
      2008 Annual Research Report
  • [Presentation] Involvement of cathepsin Bin the processing and secretion of interleukin-1β inchromogranin A-stimulated microglia2008

    • Author(s)
      Nakanishi H., et al
    • Organizer
      米国神経科学会議
    • Place of Presentation
      ワシントン DC
    • Year and Date
      2008-11-17
    • Related Report
      2008 Final Research Report
  • [Presentation] Involvement of cathepsin B in the processing and secretion of interleukin-1β in chromogranin A-stimulated microglia2008

    • Author(s)
      Nakanishi H., et al.
    • Organizer
      米国神経科学会議
    • Place of Presentation
      ワシントンDC
    • Year and Date
      2008-11-17
    • Related Report
      2008 Annual Research Report
  • [Presentation] TFAM過剰発現によるミクログリア内レドックス制御と老化に伴う脳機能低下の防止2008

    • Author(s)
      林 良憲, 他
    • Organizer
      第13回グリア研究会
    • Place of Presentation
      東京
    • Year and Date
      2008-11-08
    • Related Report
      2008 Annual Research Report 2008 Final Research Report
  • [Presentation] 細胞内染色法を用いたミクログリアならびにアストロサイト突起の微細構造の会席2008

    • Author(s)
      山田純
    • Organizer
      第13回グリア研究会
    • Place of Presentation
      東京
    • Year and Date
      2008-11-08
    • Related Report
      2008 Annual Research Report
  • [Presentation] 破骨細胞の貪食機能に着目した新たな骨破壊抑制法2008

    • Author(s)
      武 洲, 他
    • Organizer
      第50回歯科基礎医学会
    • Place of Presentation
      東京
    • Year and Date
      2008-09-24
    • Related Report
      2008 Annual Research Report 2008 Final Research Report
  • [Presentation] Inhibition of NMDA-induced outward currents by interleukin-1β in hippocampal neurons2008

    • Author(s)
      Zhang R., et al
    • Organizer
      第50回歯科基礎医学会
    • Place of Presentation
      東京
    • Year and Date
      2008-09-24
    • Related Report
      2008 Annual Research Report 2008 Final Research Report
  • [Presentation] 中高年における慢性炎症は深刻な脳炎症を引き起こす2008

    • Author(s)
      徳田 幸恵, 他
    • Organizer
      第50回歯科基礎医学会
    • Place of Presentation
      東京
    • Year and Date
      2008-09-24
    • Related Report
      2008 Annual Research Report 2008 Final Research Report
  • [Presentation] Phosphatidylserine-containing liposomes ameliorates the cytokine imbalance in the ankle joints of adjuvant arthritic rats2008

    • Author(s)
      馬紅梅, 他
    • Organizer
      第50回歯科基礎医学会
    • Place of Presentation
      東京
    • Year and Date
      2008-09-24
    • Related Report
      2008 Annual Research Report
  • [Presentation] Age-dependent differential modulation of the barrier function of the leptomeninges in the cerebral cortex by activated glial cells during the systemic inflammation2008

    • Author(s)
      Wu Z., et al
    • Organizer
      第26回国際精神神経薬理学会
    • Place of Presentation
      ミュンヘン
    • Year and Date
      2008-07-14
    • Related Report
      2008 Annual Research Report 2008 Final Research Report
  • [Presentation] Synaptic Stripping における細胞外ヌクレオチドの関与2008

    • Author(s)
      中西 博
    • Organizer
      第81回日本薬理学会総会
    • Place of Presentation
      横浜
    • Year and Date
      2008-03-17
    • Related Report
      2008 Final Research Report
  • [Presentation] Synaptic Strippingにおける細胞外ヌクレオチドの関与2008

    • Author(s)
      中西 博
    • Organizer
      第81回日本薬理学会総会、シンポジウム:細胞外ヌクレオチドによる脳機能制御一分子ダイナミクスと疾病への関与
    • Place of Presentation
      横浜
    • Year and Date
      2008-03-17
    • Related Report
      2007 Annual Research Report
  • [Presentation] Overproduction of nitric oxide by microglia due to lysosomal storage-induced p38 MAP kinase activation in cathepsin D-deficient mice2007

    • Author(s)
      Nakanishi H., et al
    • Organizer
      米国神経科学会議
    • Place of Presentation
      サンディエゴ
    • Year and Date
      2007-11-06
    • Related Report
      2008 Final Research Report
  • [Presentation] Overproduction of nitric oxide by microglia due to lysosomal storage-induced p38 MAP kinase activation in cathepsin D-deficient mice.2007

    • Author(s)
      Nakanishi H., Wu Z., and Ochi-Shindou M.
    • Organizer
      第37回北米神経科学会
    • Place of Presentation
      サンディエゴ
    • Year and Date
      2007-11-06
    • Related Report
      2007 Annual Research Report
  • [Presentation] Systemic inflammation induces age-dependent differential activation of glial cells through the leptomeninges2007

    • Author(s)
      Wu Z., et al.
    • Organizer
      第8回ヨーロッパグリア(Euroglia)会議
    • Place of Presentation
      ロンドン
    • Year and Date
      2007-09-06
    • Related Report
      2008 Final Research Report
  • [Presentation] Systemic inflammation induces age-dependent differential activation of glial cells through the leptomeninges.2007

    • Author(s)
      Wu Z. and Nakanishi H.
    • Organizer
      第8回ヨーロッパグリア(Euroglia)会議
    • Place of Presentation
      ロンドン
    • Year and Date
      2007-09-06
    • Related Report
      2007 Annual Research Report
  • [Presentation] Phosphatidylserine-containing liposomes ameliorates the cytokine imbalance in the ankle joints of adjuvant arthritic rats

    • Author(s)
      馬 紅梅, 他
    • Organizer
      第50回歯科基礎医学会
    • Place of Presentation
      東京
    • Related Report
      2008 Final Research Report
  • [Presentation] 細胞内染色法を用いたミクログリアならびにアストロサイト2008年11月8日突起の微細構造の解析

    • Author(s)
      山田 純, 他
    • Organizer
      第13回グリア研究会
    • Place of Presentation
      東京
    • Related Report
      2008 Final Research Report
  • [Book] In Neuroimmunology Research Focus2007

    • Author(s)
      Wu Z. and Nakanishi H.
    • Publisher
      Nova Science Publishers Inc
    • Related Report
      2008 Final Research Report
  • [Book] Handbook of Neurochemistry and Molecular Neurobiology2007

    • Author(s)
      Nakanishi H.
    • Publisher
      Kluwer Publishing Corporation
    • Related Report
      2008 Final Research Report
  • [Book] Age-dependent differential activation profiles of glial cells by the leptomeninges during systemic inflammationNeuroimmunology Research Focus,(Broglio PV ed)2007

    • Author(s)
      Wu Z. and Nakanishi H. (分担)
    • Publisher
      Nova Science Publishers Inc.
    • Related Report
      2007 Annual Research Report
  • [Book] Microglial Proteases: In Neural Protein Metabolism and Function. Handbook of Neurochemistry and Molecular Neurobiology, Vol.7(Lajtha A ed)2007

    • Author(s)
      Nakanishi H. (分担)
    • Publisher
      Kluwer Publishing Corporation
    • Related Report
      2007 Annual Research Report

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Published: 2007-04-01   Modified: 2016-10-28  

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