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Identification of the functional role of laminin alpha1 in ischemia.

Research Project

Project/Area Number 22790830
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeSingle-year Grants
Research Field Neurology
Research InstitutionFukushima Medical University

Principal Investigator

TOMIKAWA Naoki  福島県立医科大学, 医学部, 助教 (80468587)

Project Period (FY) 2010 – 2011
Project Status Completed (Fiscal Year 2011)
Budget Amount *help
¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2011: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2010: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Keywords神経分子病態学 / 脳梗塞 / 脳髄膜 / laminin alpha1 / 脳梗塞モデル / 新生血管 / ミクログリア / コンディショナルノックアウトマウス / laminin / 細胞外マトリックス
Research Abstract

We hypothesis that the expression of laminin alpha1 is important for mouse brain ischemia and the regeneration. To prove the hypothesis, we made mouse ischemia model and immunostained the brain. Laminin alpha1 did not expression at 6 hour after ischemia and the mainly expression was started at 24 hour after ischemia in the basement membrane of neovessel. Moreover, the expression of laminin alpha1 was observed at 7 days after ischemia which was regeneration stage. Other hand, in the lesion of ischemia, a part of microgila expressed laminin alpha1. These results indicate that laminin alpha1 associates with newly form of brain vessels after brain injury. Next, to examine whether the expression of laminin alpha1 is important for brain injury after ischemia, we generated laminin alpha1 conditional knockout(Lama1 CKO) mouse. We observed the phenotype in Lama1 CKO mice. Lama1 CKO showed markedly behavioral abnormality and we clarified that the abnormality was caused by defect of cerebellum formation using immunohistochemistry, western blot, and slice culture method. On the other hand, the apparent abnormality was not detected in the cerebrum of Lama1 CKO mice compared with wild type mice. These results indicate that it is possible to carry out the operation of ischemia model to Lama1 CKO mice. Finally, as our result, laminin alpha1 associates with the angiogenesis and the accumulation of microglia in encephalopathy and regeneration after ischemia and it is suggested that laminin alpha1 is important for the brain tissue remodeling after ischemia.

Report

(3 results)
  • 2011 Annual Research Report   Final Research Report ( PDF )
  • 2010 Annual Research Report
  • Research Products

    (21 results)

All 2012 2011 2010

All Journal Article (12 results) (of which Peer Reviewed: 6 results) Presentation (9 results)

  • [Journal Article] Laminin alpha1 is essential for mouse cerebellar development2012

    • Author(s)
      Ichikawa-Tomikawa N, Ogawa J, Douet V, Xu Z, Kamikubo Y, Sakurai T, Kohsaka S, Chiba H, Hattori N, Yamada Y, Arikawa-Hirasawa E.
    • Journal Title

      Matrix Biology

      Volume: 31 Pages: 17-28

    • Related Report
      2011 Final Research Report
  • [Journal Article] Laminin alphal is essential for mouse cerebellar development2012

    • Author(s)
      Ichikawa-Tomilkawa N, Ogawa J, Douet V, Xu Z, Kamikubo Y, Sakurai T, Kohsaka S, Chiba H, Hattori N,Yamada Y, Arikawa-Hirasawa E
    • Journal Title

      Matrix Biology

      Volume: 31 Pages: 17-28

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Possible involvement of tight junctions, extracellular matrix and nuclear receptors in epithelial differentiation2011

    • Author(s)
      Ichikawa-Tomikawa N, Sugimoto K, Satohisa S, Nishiura K. Chiba H.
    • Journal Title

      Journal of Biomedicine and Biotechnology

      Pages: 253048-253048

    • Related Report
      2011 Final Research Report
  • [Journal Article] Role of stromal microenvironment in no pharmacological resistance of CML to imatinib through Lyn/CXCR4 interactions in lipid rafts2011

    • Author(s)
      Tabe Y, Jin L, Iwabuchi K, Wang R-Y, Ichikawa N, Miida T, Cortes J, Andreeff M, Konopleva M.
    • Journal Title

      Leukemia

      Pages: 291-291

    • Related Report
      2011 Final Research Report
  • [Journal Article] Possible involvement of tight junctions, extracellular matrix and nuclear receptors in epithelial differentiation2011

    • Author(s)
      Ichikawa-Tomikawa N, Sugimoto K, Satohisa S, Nishiura K.Chiba H
    • Journal Title

      Journal of Biomedicine and Biotechnology

      Pages: 253048-253048

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Role of stromal microenvironment in nonpharmacological resistance of CML to imatinib through Lyn/CXCR4 interactions in lipid rafts2011

    • Author(s)
      Tabe Y, Jin L, Iwabuchi K, Wang R-Y, Ichikawa N, Miida T, Cortes J, Andreeff M, Konopleva M
    • Journal Title

      Leukimia

      Pages: 291-291

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Distinct mechanosensitive Ca^<2+> influx mechanisms in human primary synovial fibroblasts2010

    • Author(s)
      Sakamoto Y, Ishijima M, Kaneko H, Kurebayashi N, Ichikawa N, Futami I, Kurosawa H, Arikawa-Hirasawa E.
    • Journal Title

      Jounal of Orthopaedic Research

      Volume: 7 Pages: 859-864

    • Related Report
      2011 Final Research Report
  • [Journal Article] Perlecan deficiency causes muscle hypertrophy, a decrease in myostatin expression, and changes in muscle fiber composition2010

    • Author(s)
      Xu Z, Ichikawa N, Kosaki Y, Yamada Y, Sasaki T, Sakai LY, Kurosawa H, Hattori N, Arikawa-Hirasawa E.
    • Journal Title

      Matrix Biology

    • Related Report
      2011 Final Research Report
  • [Journal Article] Pigment epithelium-derived factor up-regulation induced by memantine, an N-methyl-d-aspartate receptor antagonist, is involved in increased proliferation of hippocampal progenitor cells2010

    • Author(s)
      Namba T, Yabe T, Gonda Y, Ichikawa N, Sanagi T, Arikawa-Hirasawa E, Mochizuki H, Kohsaka S, Uchino S.
    • Journal Title

      Neuroscience

      Volume: 167 Pages: 372-383

    • Related Report
      2011 Final Research Report
  • [Journal Article] Perlecan deficiency causes muscle hypertrophy, a decrease in myostatin expression, and changes in muscle fiber composition.2010

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

      Matrix Biology

      Volume: 29 Pages: 461-470

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Pigment epithelium-derived factor up-regulation induced by memantine, an N-methyl-D-aspartate receptor antagonist, is involved in increased proliferation of hippocampal progenitor cells.2010

    • Author(s)
      Namba T, et al.
    • Journal Title

      Neuroscience

      Volume: 167 Pages: 372-383

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Distinct mechanosensitive Ca+ influx mechanisms in human primary synovial fibroblasts.2010

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

      Journal of Orthopaedic Research

      Volume: 28 Pages: 859-864

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Presentation] Liver X receptors express in oral cancer tissues and the agonist inhibits cellular growth of oral cancer cell lines2011

    • Author(s)
      Naoki Tomikawa, Tetsuharu Kaneko, Mizuko Tanaka, Hiroshi Hasegawa, Takashi Sugino, Hideki Chiba
    • Organizer
      第70回日本癌学会学術総会
    • Place of Presentation
      名古屋
    • Year and Date
      2011-10-05
    • Related Report
      2011 Final Research Report
  • [Presentation] Laminin alpha1 is essential for the formation of the mouse cerebellar meningeal basement membrane and for cerebellar development2011

    • Author(s)
      Naoki Ichikawa-Tomikawa, Zhuo Xu, Yoshihiko Yamada, and Eri Arikawa-Hirasawa
    • Organizer
      第58回マトリックス研究会大会・第43回日本結合組織学会学術大会
    • Place of Presentation
      大分
    • Year and Date
      2011-06-10
    • Related Report
      2011 Final Research Report
  • [Presentation] Laminin alphalはマウス小脳髄膜の基底膜形成と小脳発達に重要である2011

    • Author(s)
      冨川直樹、許卓、山田吉彦、平澤恵理
    • Organizer
      第43回日本結合組織学会学術大会・第58回マトリックス研究会大会合同学術集会
    • Place of Presentation
      別府ビーコンプラザ
    • Year and Date
      2011-06-10
    • Related Report
      2011 Annual Research Report
  • [Presentation] Laminin alpha1はマウス小脳の発達に重要である2011

    • Author(s)
      冨川.市川直樹、杉野隆、田中端子、平澤恵理、千葉英樹
    • Organizer
      第100回日本病理学会総会
    • Place of Presentation
      横浜
    • Year and Date
      2011-04-29
    • Related Report
      2011 Final Research Report
  • [Presentation] Laminin alphalはマウス小脳の発達に重要である2011

    • Author(s)
      冨川直樹、杉野隆、田中端子、平澤恵理、千葉英樹
    • Organizer
      第100回日本病理学会
    • Place of Presentation
      パシフィコ横浜
    • Year and Date
      2011-04-28
    • Related Report
      2011 Annual Research Report
  • [Presentation] The role of laminin alpha1 in murine cerebellar development2010

    • Author(s)
      Naoki Tomikawa-Ichikawa, Xu Zhou, Yoshihiko, Eri Arikawa-Hirasawa
    • Organizer
      第33回日本分子生物学会年会・第83回日本生化学会大会
    • Place of Presentation
      神戸
    • Year and Date
      2010-12-08
    • Related Report
      2011 Final Research Report
  • [Presentation] The role of laminin α1 in marine cerebelluar development2010

    • Author(s)
      冨川直樹, ら
    • Organizer
      BMB2010
    • Place of Presentation
      神戸
    • Year and Date
      2010-12-08
    • Related Report
      2010 Annual Research Report
  • [Presentation] Deficiency of Lama1 causes behavioral abnormality and defects in cerebellar development in mice2010

    • Author(s)
      Naoki Ichikawa-Tomikawa, Xu Zhou, Yoshihiko, Eri Arikawa-Hirasawa
    • Organizer
      第57回マトリックス研究会大会・第42回日本結合組織学会学術大会
    • Place of Presentation
      秋田
    • Year and Date
      2010-08-19
    • Related Report
      2011 Final Research Report
  • [Presentation] Laminin alpha1欠損によるマウス小脳の発達異常2010

    • Author(s)
      冨川直樹, ら
    • Organizer
      第42回日本結合組織学会学術大会・第57回マトリックス研究会大会合同学術集会
    • Place of Presentation
      秋田
    • Related Report
      2010 Annual Research Report

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Published: 2010-08-23   Modified: 2016-04-21  

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