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Studies on factors accounting for remyelination in the central nervous system

Research Project

Project/Area Number 06670662
Research Category

Grant-in-Aid for General Scientific Research (C)

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

Principal Investigator

TSUKAMOTO Tetsuro  Fukushima Medical College Associate Professor, 医学部, 助教授 (20171978)

Co-Investigator(Kenkyū-buntansha) YAMAMOTO Teiji  Fukushima Medical College Professor, 医学部, 教授 (10106487)
Project Period (FY) 1994 – 1995
Project Status Completed (Fiscal Year 1995)
Budget Amount *help
¥2,200,000 (Direct Cost: ¥2,200,000)
Fiscal Year 1995: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 1994: ¥1,100,000 (Direct Cost: ¥1,100,000)
KeywordsMultiple Sclerosis / Myelin Formation / Nerve Tissue Culture / TNF-alpha / Astrocyte / Astrogliosis / ミエリン形成
Research Abstract

Using organotypic cultures of ICR mouse cerebellum, we studied the effects of TNF-alpha on myelin formation, and its demyelinating effects. Mature, myelinated cultures were resistant to TNF-alpha, even at the highest concentration examined, 1x4^4U/ml. However, when cultures were grown in medium containing TNF-alpha from the time of explantation, myelin formation was significantly affected at a concentration of 1x10^2U/ml. These results suggest that TNF-alpha may be involved in the remyelination block following acute myelin breakdown.
The chronic demyelinated plaque of multiple sclerosis (MS) is characterized by a loss of oligodendrocyteastrogliosis, and incomplete or no remyelinatio which probably results in part from the suppressive effects of gliotic astrocytes on myelin formation. We explanted mouse cerebella on astrocyte cultures which had benn maintained for 2 to 12 weeks and assessed the myelination in the cerebellar tissue at 18 days after explantaion. Myelination occurred vigorously in the tissue explanted on 2- to 4-week-old astrocytes, but was poorer in the tissue explanted on astrocytes older than 4 weeks. No myelin sheath was formed on 12-week-old astrocytes, although axons developed equally as well as those in the tissues explanted on 2-week-old astrocytes. As astrocytes were maintained longer, they become fibrous and immunostained more deeply with anti-glial fibrillary acidic protein antibody, being analogous to astrogliosis. These findings imply that astrogliosis in chronic demyelinated lesions of MS may potentially block remyelination.

Report

(3 results)
  • 1995 Annual Research Report   Final Research Report Summary
  • 1994 Annual Research Report
  • Research Products

    (14 results)

All Other

All Publications (14 results)

  • [Publications] Tetsuro Tsukamoto: "Suppressive effects of TNF-α on myelin formation in vitro" Acta Neurol Scand. 91. 71-75 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Tetsuro Tsukamoto: "Increased peptidylglycine α-amidating monooxygenase activity in cerebrospinal fluid of patients with multiple sclerosis" Internal Medicine. 34. 229-232 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Mikio Ishikawa: "Long-term cultured astrocytes inhibit myelin formation, but not axonal growth in the co-cultured nerve tissues" Multiple Sclerosis. (発表予定).

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Choichi Hida: "U1trastructural localization of anti-Purkinje cell antibody-binding sites in paraneoplastic cerebellar degeneration" Arch Neurol. 51. 555-558 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] 塚本哲朗: "TNF-αの髄鞘形成障害作用" 神経免疫. 2. 26-27 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] 塚本哲朗: "TNF-αによる髄鞘形成を阻害するアストロサイトの誘導" 神経免疫. 3. 74-75 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Tsukamoto T,Ishikawa M,Yamamoto T.: "Suppressive effects of TNF-alpha on myelin formation in vitro." Acta Neurol Scand. 91. 71-75 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Tsukamoto T,Noguchi M,Kayama H,Watanabe T,Asoh T,Yamamoto T.: "Increased peptidylglycine alpha-amidating monooxygenase activity in cerebrospinal fluid of patients with multiple sclerosis." Internal Med. 34. 229-232 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Ishikawa M,Tsukamoto T,Yamamoto T.: "Long-term cultured astrocytes inhibit myelin formation, but not axonal growth in the co-cultured nerve tissues." Multiple Sclerosis. (in press).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Hida C,Tsukamoto T,Awano H,Yamamoto T.: "Ultrastructural localization of anti-Purkinje cell antibody-binding sites in paraneoplastic cerebellar degeneration." Arch Neurol. 51. 555-558 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Tetsuro Tsukamoto: "Suppressive effects of TNF-α on myelin formation in vitro" Acta Neurol Scand. 91. 71-75 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Tetsuro Tsukamoto: "Increased peptidylglycine α -amidating monooxygenase activity in cerebrospinal fluid of patients with multiple sclerosis" Internal Medicine. 34. 229-232 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Mikio Ishikawa: "Long-term cultured astrocytes inhibit myelin formation of the cerebellar tissues explanted on the astrocytes" Multiple Sclerosis. (発表予定).

    • Related Report
      1995 Annual Research Report
  • [Publications] T.Tsukamoto: "Suppressive effects of TNF-α on myelin formation in vitro" Acta Neurologica Scandinavica. 91. 71-75 (1995)

    • Related Report
      1994 Annual Research Report

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Published: 1994-04-01   Modified: 2016-04-21  

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