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Functinal analysis of TGF-beta in the injured central nervous system

Research Project

Project/Area Number 23500422
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Nerve anatomy/Neuropathology
Research InstitutionTokyo Metropolitan Institute of Medical Science

Principal Investigator

KAWANO Hitoshi  公益財団法人東京都医学総合研究所, 脳発達・神経再生研究分野, 研究員 (20161341)

Co-Investigator(Kenkyū-buntansha) KURODA Junko  公益財団法人東京都医学総合研究所, 脳発達・神経再生研究分野, 研究員 (20142151)
Project Period (FY) 2011-04-28 – 2015-03-31
Project Status Completed (Fiscal Year 2014)
Budget Amount *help
¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000)
Fiscal Year 2013: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2012: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2011: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
Keywords神経再生 / 線維性瘢痕 / TGF-beta / コンドロイチン硫酸 / デルマタン硫酸 / TGF-β1 / PDGF / 脳損傷 / TGF-β / プロテオグリカン / 損傷 / グリア瘢痕
Outline of Final Research Achievements

The role of chondroitin sulfate (CS) and dermatan sulfate (DS) was examined in mice after transection of nigrostriatal dopaminergic pathway and treatment with of glycosaminoglycan degrading enzymes. Two weeks after injury, fibrotic and glial scars were formed around the lesion and transected axons did not regenerate beyond the lesion. Injection of chondroitinase B. which degrades DS, into the lesion site completely suppressed the fibrotic scar formation, reduced the glial scar and promoted the regeneration of dopaminergic axons. In contrast, injection of chondroitinase AC, a CS-degrading enzyme, did not suppress the fibrotic scar formation, but promoted the axonal regeneration. These results first demonstrate that DS and CS play different functions after CNS injury: DS is involved in the lesion scar formation and CS inhibits axonal regeneration (Li et al., 2013).

Report

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

    (27 results)

All 2014 2013 2012 2011 Other

All Journal Article (12 results) (of which Peer Reviewed: 11 results) Presentation (14 results) Remarks (1 results)

  • [Journal Article] Roles of chondroitin sulfate and dermatan sulfate in the formation of a lesion scar and axonal regeneration after traumatic injury of the mouse brain.2013

    • Author(s)
      Li HP, Komuta Y, Kimura-Kuroda J, van Kuppevelt TH, Kawano H
    • Journal Title

      J. Neurotrauma

      Volume: 30 Issue: 5 Pages: 413-425

    • DOI

      10.1089/neu.2012.2513

    • Related Report
      2013 Research-status Report 2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] RP58 regulates the multipolar-bipolar transition of newborn neurons in the developing cerebral cortex.2013

    • Author(s)
      Ohtaka-Maruyama C, Hirai S, Miwa A, Heng JI, Shitara H, Ishii R, Taya C, Kawano H, Kasai M, Nakajima K, Okado H.
    • Journal Title

      Cell Rep

      Volume: 3(2) Issue: 2 Pages: 458-71

    • DOI

      10.1016/j.celrep.2013.01.012

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] N-acetylgalactosaminyl-transferase-1 inhibits recovery from neural injury.2013

    • Author(s)
      Kosei Takeuchi, Nozomu Yoshioka, Susumu Higa Onaga, Yumi Watanabe, et. al.
    • Journal Title

      Nature Communications

      Volume: 4 Issue: 1 Pages: 2740-2740

    • DOI

      10.1038/ncomms3740

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] The astrocytic lineage marker calmodulin-regulated spectrin-associated protein 1 (Camsap1) : phenotypic heterogeneity of newly born Camsapl-expressing cells in injured mouse brain2012

    • Author(s)
      Yoshioka Nozomu, Asou Hiroaki, Hisanaga Shin-ichi, Kawano Hitoshi
    • Journal Title

      J Comp Neurol

      Volume: 520 Issue: 6 Pages: 1301-1317

    • DOI

      10.1002/cne.22788

    • Related Report
      2012 Research-status Report 2011 Research-status Report
    • Peer Reviewed
  • [Journal Article] Nicotine-like effects of the neonicotinoid insecticides acetamiprid and imidacloprid on cerebellar neurons from neonatal rats2012

    • Author(s)
      Junko Kimura-Kuroda
    • Journal Title

      PLoS ONE

      Volume: 7 Issue: 2 Pages: e32432-e32432

    • DOI

      10.1371/journal.pone.0032432

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] LMTK1/AATYK1 is a novel regulator of axonal outgrowth that acts via Rab11 in a Cdk5-dependent manner.2012

    • Author(s)
      Takano T, Tomomura M, Yoshioka N, Tsutsumi K, Terasawa Y, Saito T, Kawano H, Kamiguchi H, Fukuda M, Hisanaga S
    • Journal Title

      J. Neurosci.

      Volume: 32 Pages: 6587-6599

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Role of the lesion scar in the response to damage and repair of the central nervous system.2012

    • Author(s)
      3) Kawano H, Kimura-Kuroda J, Komuta Y, Yoshioka N, Li HP, Kawamura K, Li Y, Raisman G
    • Journal Title

      Cell Tissue Res.

      Volume: 349 Issue: 1 Pages: 169-180

    • DOI

      10.1007/s00441-012-1336-5

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Localization of papillofoveal bundles in primates2012

    • Author(s)
      Hiraoka M, Inoue K, Kawano H, Takada M
    • Journal Title

      Anat Rec

      Volume: 295 Issue: 2 Pages: 347-354

    • DOI

      10.1002/ar.21519

    • Related Report
      2011 Research-status Report
    • Peer Reviewed
  • [Journal Article] Nicotine-like effects of the neonicotinoid insecticides acetamiprid and imidacloprid on cerebellar neurons of neonatal rats.2012

    • Author(s)
      Kimura-Kuroda J, Komuta Y, Kuroda Y, Hayashi M, Kawano H
    • Journal Title

      PloS One

      Volume: 7

    • Related Report
      2011 Research-status Report
    • Peer Reviewed
  • [Journal Article] Role of the lesion scar in the response to damage and repair of the central nervous system.2012

    • Author(s)
      Kawano H, Kimura-Kuroda J, Komuta Y, Yoshioka N, Li HP, Kawamura K, Li Y, Raisman G
    • Journal Title

      Cell and Tissue Research

      Volume: in press Pages: 1-12

    • Related Report
      2011 Research-status Report
    • Peer Reviewed
  • [Journal Article] Small molecule inhibitor of type I transforming growth factor-β receptor kinase a meliorates inhibitory milieu in injured brain and promotes regeneration of nigrostriatal dopaminergic axons2011

    • Author(s)
      Yoshioka Nozomu, Kimura-Kuroda Junko, Saito Tarou, Kawamura Koki, Hisanaga Shin-ichi, Kawano Hitoshi
    • Journal Title

      J Neurosci Res

      Volume: 89 Issue: 3 Pages: 381-393

    • DOI

      10.1002/jnr.22552

    • Related Report
      2011 Research-status Report
    • Peer Reviewed
  • [Journal Article] 脊髄損傷後の軸索再生と組織修復-グリア瘢痕と線維性瘢痕の作用2011

    • Author(s)
      川野 仁、木村-黒田純子、小牟田 縁 吉岡 望
    • Journal Title

      脳21

      Volume: 14 Pages: 15-19

    • Related Report
      2011 Research-status Report
  • [Presentation] Exposure of neonicotinoid pesticide disrupts gene expression profiles in cerebellar cultures from neonatal rats -possible causal factors for developmental disorders-2014

    • Author(s)
      Junko Kimura-Kuroda、Yasumasa Nishito, Hiroko Yanagisawa, Yoichiro Kuroda, Yukari Komuta, Hitoshi Kawano, Masaharu Hayashi
    • Organizer
      37th Annual Meeting of the Japan Neuroscience Society
    • Place of Presentation
      Yokohama, Japan
    • Year and Date
      2014-09-11 – 2014-09-13
    • Related Report
      2014 Annual Research Report
  • [Presentation] 中枢神経系の損傷部におけるコンドロイチン硫酸の免疫組織化学的局在についての考察2012

    • Author(s)
      川野 仁、小牟田 縁、吉岡 望、李 洪鵬、滕 錫川
    • Organizer
      第117回日本解剖学会総会
    • Place of Presentation
      山梨大学
    • Related Report
      2011 Research-status Report
  • [Presentation] 線維芽細胞のTGF-β1に対する感受性の生後発達2012

    • Author(s)
      小牟田緑、木村-黒田純子、川野 仁
    • Organizer
      第117回日本解剖学会総会
    • Place of Presentation
      山梨大学
    • Related Report
      2011 Research-status Report
  • [Presentation] 中枢神経系における組織修復と神経再生阻害のメカニズムについて2011

    • Author(s)
      吉岡 望、阿相皓晃、木村ー黒田純子、久永眞一、川野 仁
    • Organizer
      神経組織の成長・再生・移植研究会
    • Place of Presentation
      東京医科大学病院
    • Related Report
      2011 Research-status Report
  • [Presentation] 脳外傷後の組織修復と神経再生阻害に果たす瘢痕組織の役割について2011

    • Author(s)
      吉岡 望、阿相皓晃、木村ー黒田純子、久永眞一、川野 仁
    • Organizer
      第34回日本神経科学大会
    • Place of Presentation
      パシフィコ横浜
    • Related Report
      2011 Research-status Report
  • [Presentation] 生後の発生に依存した線維性瘢痕形成機構の研究2011

    • Author(s)
      小牟田縁、木村ー黒田純子、柳澤比呂子、三五一憲、川野 仁
    • Organizer
      第34回日本神経科学大会
    • Place of Presentation
      パシフィコ横浜
    • Related Report
      2011 Research-status Report
  • [Presentation] 脳外傷後の組織修復と神経再生阻害に果たす瘢痕組織の役割について2011

    • Author(s)
      吉岡 望、阿相皓晃、木村ー黒田純子、久永眞一、川野 仁
    • Organizer
      第54回神経化学会
    • Place of Presentation
      石川県加賀市
    • Related Report
      2011 Research-status Report
  • [Presentation] 損傷後の脳における線維性瘢痕の形成と軸索再生の阻害について

    • Author(s)
      川野 仁、木村-黒田純子、小牟田縁、吉岡 望、武内恒成
    • Organizer
      第23回日本神経科学大会
    • Place of Presentation
      京都
    • Related Report
      2013 Research-status Report
  • [Presentation] The fibrotic scar is a major impediment for axonal regeneration after traumatic brain injury.

    • Author(s)
      Hitoshi Kawano, Junko Kimura-Kuroda, Yukari Komuta, Hong-Peng Li and Kosei Takeuchi
    • Organizer
      34th Annual Meeting of Australian Neuroscience Society
    • Place of Presentation
      Adelaide, Australia
    • Related Report
      2013 Research-status Report
  • [Presentation] The fibrotic scar is a major impediment for axonal regeneration after traumatic brain injury.

    • Author(s)
      Hitoshi Kawano, Junko Kimura-Kuroda, Yukari Komuta, Hong-Peng Li and Kosei Takeuchi
    • Organizer
      10th World Congress on Brain Injury.
    • Place of Presentation
      San Fransisco, USA
    • Related Report
      2013 Research-status Report
  • [Presentation] マウス損傷脳における瘢痕形成と軸索再生に対するコンドロイチン硫酸とデルマタン硫酸の役割

    • Author(s)
      川野 仁、小牟田 縁、李 洪鵬、木村-黒田純子
    • Organizer
      第35回日本神経科学大会
    • Place of Presentation
      名古屋国際会議場
    • Related Report
      2012 Research-status Report
  • [Presentation] 脳損傷後の瘢痕形成と軸索再生に対する細胞外マトリックスの役割

    • Author(s)
      川野 仁、小牟田 縁、木村-黒田純子
    • Organizer
      第118回日本解剖学会総会
    • Place of Presentation
      かがわ会議場
    • Related Report
      2012 Research-status Report
  • [Presentation] Postnatal development of the fibrotic scar formation: an in vitro study.

    • Author(s)
      Komuta Y, Kimura-Kuroda J, Kawano H
    • Organizer
      FENS 2012
    • Place of Presentation
      Barcelona
    • Related Report
      2012 Research-status Report
  • [Presentation] Axon regeneration in the mice lacking in the enzymes synthesizing chondroitin sulfate.

    • Author(s)
      Takeuchi K, Higa-Onaga S, Yoshioka N, Kudo C, Kawano H, Igarashi M
    • Organizer
      FENS 2012
    • Place of Presentation
      Barcelona
    • Related Report
      2012 Research-status Report
  • [Remarks]

    • URL

      http://www.igakuken.or.jp/regeneration/

    • Related Report
      2011 Research-status Report

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Published: 2011-08-05   Modified: 2019-07-29  

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