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Mechanism of axon guidance after injury to the central nervous system.

Research Project

Project/Area Number 15390438
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Cerebral neurosurgery
Research InstitutionChiba University

Principal Investigator

YAMASHITA Toshihide  Chiba University, Graduate School of Medicine, Professor, 大学院・医学研究院, 教授 (10301269)

Project Period (FY) 2003 – 2005
Project Status Completed (Fiscal Year 2005)
Budget Amount *help
¥14,100,000 (Direct Cost: ¥14,100,000)
Fiscal Year 2005: ¥4,100,000 (Direct Cost: ¥4,100,000)
Fiscal Year 2004: ¥4,800,000 (Direct Cost: ¥4,800,000)
Fiscal Year 2003: ¥5,200,000 (Direct Cost: ¥5,200,000)
Keywordsregeneration / neuron / axon / glia / cell / protein
Research Abstract

To explore the mechanism of axon guidance of the injured neurons in the cetral nervous system (CNS), we screened the genes whose expression was changed after stimulation with neurotrophins using microarray technique. We got more than one hundred genes that showed enhanced expression. We focus on several genes that are expected to play a role in axon guidance, and decide to perform detailed analysis. We found that chimaerins are involved in desensitization of the neurons to some inhibitory molecules. The expression of chimaerins are enhanced in the cerebellar granule neurons after exposure to neurotrophins. When chimaerins are ectopically overexpressed, inhibition of neurite outgrowth by myelin-associated glycoprotein is reduced to the control level. In contrast, the effect of prior exposure to neurotrophins is abolished by the gene knockdown of chimaerins using siRNA. Thus, chimaerins may promote axon regeneration after injury to the CNS. In addition, we are interested in another gene, repulsive guidance molecule (RGM). RGMa inhibits mammalian CNS neurite outgrowth by a mechanism dependent on the activation of the Rho/Rho-kinase pathway. RGMa expression is observed in oligodendrocytes, myelinated fibers, and neurons of the adult rat spinal cord, and is induced around the injury site following spinal cord injury. We developed an antibody to RGMa that efficiently blocks the effect of RGMa in vitro. Intrathecal administration of the antibody to rats with thoracic spinal cord hemisection results in significant axonal growth of the corticospinal tract, and improves functional recovery. Thus, RGMa plays an important role in limiting axonal regeneration after CNS injury, and the RGMa antibody offers a possible therapeutic agent in clinical conditions characterized by a failure of CNS regeneration.

Report

(4 results)
  • 2005 Annual Research Report   Final Research Report Summary
  • 2004 Annual Research Report
  • 2003 Annual Research Report
  • Research Products

    (37 results)

All 2005 2004 Other

All Journal Article (37 results)

  • [Journal Article] Wallerian degeneration involves Rho/Rho-kinase signaling.2005

    • Author(s)
      山岸覚
    • Journal Title

      Journal of Biological Chemistry 280

      Pages: 20384-20388

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Annual Research Report 2005 Final Research Report Summary
  • [Journal Article] Binding of soluble myelin-associated glycoprotein to specific gangliosides induces the association of p75^NTR to lipid rafts and signal transduction.2005

    • Author(s)
      藤谷昌司
    • Journal Title

      Journal of Neurochemistry 94

      Pages: 15-21

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Biological activity of neruotrophins is dependent on recruitment of Racl to lipid rafts.2005

    • Author(s)
      藤谷昌司
    • Journal Title

      Biochem. Biophys. Res. Commun. 327

      Pages: 150-154

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] c-Jun N-terminal kinase activation in dorsal root ganglion contributes to pain hypersensivity.2005

    • Author(s)
      銅冶英雄
    • Journal Title

      Biochem. Biophys. Res. Commun. 335

      Pages: 132-138

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] ERK MAP kinase activation in dorsal root ganglion (DRG) and the spinal cord following DRG injury in rats.2005

    • Author(s)
      銅冶英雄
    • Journal Title

      Spine 30

      Pages: 2252-2256

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Wallerian degeneration involves Rho/Rho-kinase signaling.2005

    • Author(s)
      Yamagishi, S., Fujitani, M., Hata, K., Kitajo, K., Mimura, F., Abe, H., Yamashita, T.
    • Journal Title

      J.Biol.Chem. 280

      Pages: 20384-20388

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Binding of soluble myelin associated glycoprotein to specific gangliosides induces the association of p75NTR to lipid rafts and signal transduction.2005

    • Author(s)
      Fujitani, M., Kawai, H., Proia, R.L., Kashiwagi, A., Yasuda, H., Yamashita, T.
    • Journal Title

      J.Neurochem. 94

      Pages: 15-21

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Biological activity of neurotrophins is dependent on recruitment of Rac1 to lipid rafts.2005

    • Author(s)
      Fujitani, M., Honda, A., Hata, K., Yamagishi, S., Tohyama, M., Yamashita, T.
    • Journal Title

      Biochem.Biophys.Res.Commun. 327

      Pages: 150-154

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] c-Jun N-terminal kinase activation in dorsal root ganglion contributes to pain hypresensitivity.2005

    • Author(s)
      Doya, H., Ohtori, S., Fujitani, M., Saito, T., Hata, K., Ino, H., Takahashi, K., Moriya, H., Yamashita, T.
    • Journal Title

      Biochem.Biophys.Res.Commun. 335

      Pages: 132-138

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] ERK MAP kinase activation in the dorsal root ganglion (DRG) and the spinal cord following DRG injury in rats.2005

    • Author(s)
      Doya, H., Ohtori, S., Takahashi, Ka., Aoki, Y., Ino, H., Takahashi, Y., Moriya, H., Yamashita, T.
    • Journal Title

      Spine 30

      Pages: 2252-2256

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Binding of soluble myelin-associated glycoprotein to specific gangliosides induces the association of p75^<NTR> to lipid rafts and signal transduction.2005

    • Author(s)
      藤谷昌司
    • Journal Title

      Journal of Neurochemistry 94

      Pages: 15-21

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Biological activity of neurotrophins is dependent on recruitment of Rac1 to lipid rafts.2005

    • Author(s)
      藤谷昌司
    • Journal Title

      Biochem.Biophys.Res.Commun. 327

      Pages: 150-154

    • Related Report
      2005 Annual Research Report
  • [Journal Article] c-Jun N-terminal kinase activation in dorsal root ganglion contributes to pain hypersensitivity.2005

    • Author(s)
      銅冶英雄
    • Journal Title

      Biochem.Biophys.Res.Commun. 335

      Pages: 132-138

    • Related Report
      2005 Annual Research Report
  • [Journal Article] ERK MAP kinase activation in the dorsal root ganglion (DRG) and the spinal cord following DRG injury in rats.2005

    • Author(s)
      銅冶英雄
    • Journal Title

      Spine 30

      Pages: 2252-2256

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Promotion of axon regeneration by MAG and Nogo through divergent signals downstream of G/G2004

    • Author(s)
      長谷川結子
    • Journal Title

      Journal of Neuroscience 24・30

      Pages: 6826-6832

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary 2004 Annual Research Report
  • [Journal Article] Activation of Rho in the injured axons following spinal cord injury.2004

    • Author(s)
      Tomas Madura
    • Journal Title

      EMBO Reports 5・4

      Pages: 412-417

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary 2004 Annual Research Report
  • [Journal Article] EphA receptors direct the differentiation of mammalian neural precursor cells through Ras/MAPK nathway2004

    • Author(s)
      青木美和
    • Journal Title

      Journal of Biological Chemistry 279・31

      Pages: 32643-32650

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] P311 accelerates nerve regeneration of the axotomized facial nerve.2004

    • Author(s)
      藤谷昌司
    • Journal Title

      Journal of Neurochemistry 91・3

      Pages: 737-744

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary 2004 Annual Research Report
  • [Journal Article] Chimaerins act downstream from neurotrophins in overcoming inhibition of neurite outgrowth by MAG.2004

    • Author(s)
      水野龍吉
    • Journal Title

      Journal of Neurochemistry 91・2

      Pages: 395-403

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary 2004 Annual Research Report
  • [Journal Article] Cytoplasmic p21^Cip/WAF1 enhances axonal regeneration and functional recovery after spinal cord injury in rats.2004

    • Author(s)
      田中裕之
    • Journal Title

      Neuroscience 127・1

      Pages: 155-164

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Promotion of axon regeneration by MAG and Nogo through divergent signals downstream of G_i/G.2004

    • Author(s)
      Hasegawa, Y., Fujitani, M., Hata, K., Tohyama, M., Yamagishi, S., Yamashita, T.
    • Journal Title

      J.Neurosci. 24-30

      Pages: 6826-6832

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Activation of Rho in the injured axons following spinal cord injury.2004

    • Author(s)
      Madura, T., Yamashita, T., Kubo, T., Fujitani, M., Hosokawa, K., Tohyama, M.
    • Journal Title

      EMBO Reports 5-4

      Pages: 412-417

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] EphA receptors direct the differentiation of mammalian neural precursor cells through Ras/MAPK pathway.2004

    • Author(s)
      Aoki, M., Yamashita, T., Tohyama, M.
    • Journal Title

      J.Biol.Chem. 279-31

      Pages: 32643-32650

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] P311 accelerates nerve regeneration of the axotomized facial nerve.2004

    • Author(s)
      Fujitani, M., Yamagishi, S., Che, Y.-H., Hata, K., Kubo, T., Ino, H., Tohyama, M., Yamashita.T.
    • Journal Title

      J.Neurochem. 91-3

      Pages: 737-744

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Chimaerins act downstream from neurotrophins in overcoming inhibition of neurite outgrowth by MAG.2004

    • Author(s)
      Mizuno, T., Yamashita, T., Tohyama, M.
    • Journal Title

      J.Neurochem. 91-2

      Pages: 395-403

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Cytoplasmic p21^<Cip1/WAF1> enhances axonal regeneration and functional recovery after spinal cord injury in rats.2004

    • Author(s)
      Tanaka, H., Yamashita, T., Yachi, K, Fujiwara, K., Yoshikawa, K., Tohyama, M.
    • Journal Title

      Neuroscience 127-1

      Pages: 155-164

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] EphA receptors direct the differentiation of mammalian neural precursor cells through RAS/MAPK pathway.2004

    • Author(s)
      青木美和
    • Journal Title

      Journal of Biological Chemistry 279・31

      Pages: 32643-32650

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Cytoplasmic P21^<Cip1/WAF1> enhances axonal regeneration and functional recovery after spinal cord injury in rats.2004

    • Author(s)
      田中裕之
    • Journal Title

      Neuroscience 127・1

      Pages: 155-164

    • Related Report
      2004 Annual Research Report
  • [Journal Article] RGMa inhibition promotes axonal growth and recovery after spinal cord injury.

    • Author(s)
      羽田克彦
    • Journal Title

      Journal of Cell Biol. 印刷中

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Delayed treatment with Rho-kinase inhibitor does not enhance axonal regeneration for functional recovery after spinal cord injury in rats.

    • Author(s)
      西尾豊
    • Journal Title

      Exp. Neurol. 印刷中

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Rho-kinase inhibitor enhance axonal regeneration and functional recovery after peripheral nerve injury.

    • Author(s)
      平賀晃之
    • Journal Title

      J. Peripher. Nerv. Syst. 印刷中

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Adenoviral Gene Transfer in the Peripheral Nervous System.

    • Author(s)
      渡辺(齊藤)朋子
    • Journal Title

      J. Orthopaedic Sci.

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] RGMa inhibition promotes axonal growth and recovery after spinal cord injury.

    • Author(s)
      Hata, K., Fujitani, M., Yasuda, Y., Doya, H., Saito, T., Yamagishi, S., Mueller, B.K., Yamashita.T.
    • Journal Title

      J.Cell Biol. (In press)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Delayed treatment with Rho-kinase inhibitor does not enhance axonal regeneration or functional recovery after spinal cord injury in rats.

    • Author(s)
      Nishio, Y., Koda, M., Kitajo, K, Seto, M., Hata, K., Taniguchi, J., Moriya, H., Fujitani, M., Kubo, T., Yamashita, T.
    • Journal Title

      Exp.Neurol. (In press)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Rho-kinase inhibition enhances axonal regeneration and functional recovery after peripheral nerve injury.

    • Author(s)
      Hiraga, A., Kuwabara, S., Douya, BL, Kanai, K., Fujitani, M., Taniguchi, J., Arai, K., Mori, M., Hattori, T., Yamashita, T.
    • Journal Title

      J.Peripher.Nerv.Syst. (In press)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Adenoviral Gene Transfer in the Peripheral Nervous System.

    • Author(s)
      Saito-Watanabe, T., Ohtori, S., Koda, M., Aoki, Y., Doya, H., Shirasawa, H., Yamazaki, M., Moriya, H., Takahashi, K., Yamashita, T.
    • Journal Title

      J.Orthopaedic Sci. (In press)

    • NAID

      10017328880

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Adenoviral Gene Transfer in the Peripheral Nervous System.

    • Author(s)
      渡辺(齋藤)朋子
    • Journal Title

      J.Orthopaedic Sci. (印刷中)

    • Related Report
      2005 Annual Research Report

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Published: 2003-04-01   Modified: 2016-04-21  

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