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Anti-apoptotic Therapy (Intrathecal Injection of Anti-apoptotic PTD-FNK Protein) in a Mouse Model of Amyotrophic Lateral Sclerosis

Research Project

Project/Area Number 17590879
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Neurology
Research InstitutionOkayama University

Principal Investigator

TAKEHISA Yasushi  Okayama University Hospital of Medicine and Dentistry, Research Associates, 医学部・歯学部附属病院, 助手 (00379752)

Co-Investigator(Kenkyū-buntansha) ABE Koji  Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Professor, 大学院医歯薬学総合研究科, 教授 (20212540)
NAGAI Makiko  Okayama University Hospital of Medicine and Dentistry, Research Associates, 医学部・歯学部附属病院, 助手 (80420488)
HAYASHI Takeshi  Okayama University Hospital of Medicine and Dentistry, Research Associates, 医学部・歯学部附属病院, 助手 (40314679)
MURAKAMI Tetsuro  Okayama University Hospital of Medicine and Dentistry, Research Associates, 医学部・歯学部附属病院, 助手 (70403475)
瓦林 毅  岡山大学, 医学部・歯学部附属病院, 助手 (90186156)
Project Period (FY) 2005 – 2006
Project Status Completed (Fiscal Year 2006)
Budget Amount *help
¥3,100,000 (Direct Cost: ¥3,100,000)
Fiscal Year 2006: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 2005: ¥1,800,000 (Direct Cost: ¥1,800,000)
KeywordsALS / ant-apoptotic therapy / neural precursor cell / IGF-1 / neurotrophic factors / FNK / intrathecal infusion / SODG93A transgenic mice / 抗アポトーシス治療法 / 筋萎縮性側索硬化症(ALS)
Research Abstract

We investigated three steps of neural precursor cell activation-proliferation, migration, and differentiation.in amyotrophic lateral sclerosis spinal cord treated with intrathecal infusion of epidermal growth factor (EGF) and fibroblast growth factor 2 (FGF2) into the lumbar spinal cord region of normal and symptomatic transgenic (Tg) mice with a mutant human Cu/Zn superoxide disniutase (SOD1) gene. We observed that 5-bromodeoxyuridine (BrdU) + nestin double-labeled neural precursor cells increased in the spinal cords of Tg mice compared with non-Tg mice, with a much greater increase produced by EGF and FGF2 treatment. The number of BrdU + nestin double-labeled cells was larger than that of BrdU + ionized calcium-binding adapter molecule.1 (Ibal), BrdU + glial fibrillary acidic protein (GFAP). or BrdU + highly polysialylated neural cell adhesion molecule (.PSA-NCAM.) double-labeled cells, but none expressed neuronal nuclear antigen (NeuN). On further analysis of the gray matter of Tg mice, the number of BrdU + nestin and BrdU + PSA-NCAM double-labeled cells increased more in the ventral horns than the dorsal horns. which was again greatly enhanced by EGF and FGF2 treatment. Because neural precursor cells reside close to the ependyma of central canal, the present study suggests that proliferation and migration of neural precursor cells to the ventral horns is greatly activated in symptomatic Tg mice and is further enhanced by EGF and FGF2 treatment and, furthermore, that the neural precursor cells preferentially differentiate into neuronal precursor cells instead of astrocytes in Tg mice with EGF and FGF2 treatment.

Report

(3 results)
  • 2006 Annual Research Report   Final Research Report Summary
  • 2005 Annual Research Report
  • Research Products

    (15 results)

All 2007 2006 2005 Other

All Journal Article (15 results)

  • [Journal Article] PINK1, a gene product of PARK6, accumulates in □-synucleinopathy brains.2007

    • Author(s)
      Murakami T, Moriwaki Y, Kawarabayashi T, Nagai M, Ohta, Y, Deguchi K, Kurata T, Takehisa Y, Matsubara E, Ikeda M, Harigaya Y, Shoji M, Takahashi R, Abe
    • Journal Title

      J Neurol Neurosurg Psychiatry. 8(Epub ahead of prin)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Early decrease of mitochondrial DNA repair enzymes in spinal motor neurons of presymptomatic transgenic mice carrying a mutant SOD1 gene.2007

    • Author(s)
      Murakami T, Nagai M, Miyazaki K, Morimoto N, Ohta Y, Kurata T, Takehisa Y, Kamiya T, Abe K
    • Journal Title

      Brain Res. 8(Epub ahead of prin)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Protein-bound crotonaldehyde accumulates in the spinal cord of superoxide dismutase-1 mutation- associated familial amyotrophic lateral sclerosis and its transgenic mouse model.2007

    • Author(s)
      Shibata N, Kawaguchi M, Uchida K, Kakita A, Takahashi H, Nakano R, Fujimura H, Sakoda S, Ihara Y, Nobukuni K, Takehisa Y, Kuroda S, Kokubo Y, Kuzuhara S, Honma T, Mochizuki Y, Mizutani T, Yamada S, Toi S, Sasaki S, Iwata M, Hirano A, Yamamoto T, Kato Y, Sawada T, Kobayashi M
    • Journal Title

      Neuropathology. 27

      Pages: 49-61

    • NAID

      10021235172

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] PINK1, a gene product of PARK6, accumulates in □-synucleinopathy brains.2007

    • Author(s)
      Murakami T, Moriwaki Y, Kawarabayashi T, Nagai M, Ohta Y, Deguchi K, Kurata T, Takehisa Y, Matsubara E, Ikeda M, Harigaya Y, Shoji M, Takahashi R, Abe
    • Journal Title

      J Neurol Neurosurg Psychiatry. 8

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Early decrease of mitochondrial DNA repair enzymes in spinal motor neurons of presymptomatic transgenic mice carrying a mutant SOD1 gene.2007

    • Author(s)
      Murakami T, Nagai M, Miyazaki K, Morimoto N, Ohta Y, Kurata T, Takehisa Y, Kamiya T, Abe K.
    • Journal Title

      Brain Res. 8

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Protein-bound crotonaldehyde accumulates in the spinal cord of superoxide dismutase-1 mutation-associated familial amyotrophic lateral sclerosis and its transgenic mouse model.2007

    • Author(s)
      Shibata N, Kawaguchi M, Uchida K, Kakita A, Takahashi H, Nakano R, Fujimura H, Sakoda S, Ihara Y, Nobukuni K, Takehisa Y, Kuroda S, Kokubo Y, Kuzuhara S, Honma T, Mochizuki Y, Mizutani T, Yamada S, Toi S, Sasaki S, Iwata M, Hirano A, Yamamoto T, Kato Y, Sawada T, Kobayashi M.
    • Journal Title

      Neuropathology. 27

      Pages: 49-61

    • NAID

      10021235172

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] PINK1, a gene product of PARK6, accumulates in □-synucleinopathy brains.2007

    • Author(s)
      Murakami T, Moriwaki Y, Kawarabayashi T, Nagai M, Ohta Y, Deguchi K, Kurata T, Takehisa Y, Matsubara E, Ikeda M, Harigaya Y, Shoji M, Takahashi R, Abe
    • Journal Title

      J Neurol Neurosurg Psychiatry. 8 (Epub ahead of prin)

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Early decrease of mitochondrial DNA repair enzymes in spinal motor neurons of presymptomatic transgenic mice carrying a mutant SOD1 gene.2007

    • Author(s)
      Murakami T, Nagai M, Miyazaki K, Morimoto N, Ohta Y, Kurata T, Takehisa Y, Kamiya T, Abe K.
    • Journal Title

      Brain Res. 8 (Epub ahead of prin)

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Protein-bound crotonaldehyde accumulates in the spinal cord of superoxide dismutase-1 mutation-associated familial amyotrophic lateral sclerosis and its transgenic mouse model.2007

    • Author(s)
      Shibata N, Kgwaguchi M, Uchida K, Kakita A, Takahashi H, Nakano R, Fujimura H, Sakoda S, Ihara Y, Nobukuni K, Takehisa Y, Kuroda S, Kokubo Y, Kuzuhara S, Honma T, Mochizuki Y, Mizutani T, Yamada S, Toi S, Sasaki S, Iwata M, Hirano A, Yamamoto T, Kato Y, Sawada T, Kobayashi M.
    • Journal Title

      Neuropathology. 27

      Pages: 49-61

    • NAID

      10021235172

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Intrathecal injection of epidermal growth factor and fibroblast growth factor 2 promotes proliferation of neural precursor cells in the spinal cords of mice with mutant human SOD1 gene.2006

    • Author(s)
      Ohta Y, Nagai M, Nagata T, Murakami T, Nagano I, Narai H, Kurata T, Shiote M, Shoji M, Abe K
    • Journal Title

      J. Neurosci. Res. 84

      Pages: 980-992

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Intrathecal injection of epidermal growth factor and fibroblast growth factor 2 promotes proliferation of neural precursor cells in the spinal cords of mice with mutant human SOD1 gene.2006

    • Author(s)
      Ohta Y, Nagai M, Nagata T, Murakami T, Nagano I, Narai H, Kurata T, Shiote M, Shoji M, Abe K.
    • Journal Title

      J. Neurosci. Res. 84

      Pages: 980-992

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Beneficial effects of intrathecal IGF-1 administration in patients with amyotrophic lateral sclerosis.2005

    • Author(s)
      Nagano I, Shiote M, Murakami T, Shoji M, Abe K.
    • Journal Title

      Neurol Res 27(7)

      Pages: 768-772

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Therapeutic benefit of intrathecal injection of insulin-like growth factor-1 in a mouse model of Amyotrophic Lateral Sclerosis.2005

    • Author(s)
      Nagano I, Ilieva H, Shiote M, Murakami T, Yokoyama M, Shoji M, Abe K.
    • Journal Title

      J Neurol Sci 235(1-2)

      Pages: 61-68

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Prevention of spinal motor neuron death by insulin-like growth factor-1 associating with the signal transduction systems in SODG93A transgenic mice.2005

    • Author(s)
      Narai H, Nagano I, Ilieva H, Shiote M, Nagata T, Hayashi T, Shoji M, Abe K.
    • Journal Title

      J Neurosci Res 15・82

      Pages: 452-457

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Intrathecal injection of epidermal growth factor and fibroblast growth factor 2 promotes proliferation of neural precursor cells in the spinal cords of mice with mutant human SOD1 gene

    • Author(s)
      Ohta Y, Nagai M, Nagata T, Murakami T, Nagano I, Narai H, Kurata T, Shiote M, Shoji M, Abe K.
    • Journal Title

      J. Neurosci. Res. 8 4

      Pages: 980-992

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary

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Published: 2005-04-01   Modified: 2016-04-21  

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