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Development of the agents to stimulate neurotrophin synthesis -An approach for spinal cord regeneration-

Research Project

Project/Area Number 11557111
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section展開研究
Research Field Orthopaedic surgery
Research InstitutionAichi Bunkyo Women's College

Principal Investigator

FURUKAWA Yoshiko  Aichi Bunkyo Women' s College, Professor, 教授 (20219108)

Co-Investigator(Kenkyū-buntansha) 新田 淳美  岐阜薬科大学, 薬学部, 助手 (20275093)
岩田 章子  愛知文教女子短期大学, 助教授 (20149503)
古川 昭栄  岐阜薬科大学, 薬学部, 教授 (90159129)
Project Period (FY) 1999 – 2001
Project Status Completed (Fiscal Year 2001)
Budget Amount *help
¥11,800,000 (Direct Cost: ¥11,800,000)
Fiscal Year 2001: ¥3,300,000 (Direct Cost: ¥3,300,000)
Fiscal Year 2000: ¥3,200,000 (Direct Cost: ¥3,200,000)
Fiscal Year 1999: ¥5,300,000 (Direct Cost: ¥5,300,000)
Keywordsimmunosuppressive drugs / neurotrophic factors / spinal cord injury / neuroprotection / nerve regeneration / injury restoration / 免疫抑制剤 / イムノフィリンリガンド / 脊髄 / 神経栄養因子 / 免疫組織染色法 / 抗ペプチド抗体 / 再生 / NGF / エンザイムイムノアッセイ法 / RT-PCR法
Research Abstract

Immunophilin ligands have been reported to possess neurotrophic activities including neurite-promoting activity in addition to well-known inimunosuppressive actions, but the mechanisms under the neurotrophic effects remain unknown. We presumed that immunophilin ligands show the neurotrophic actions by the regulation of synthesis of neurotrophic factors, and examined this possibility by in vitro and in vivo experiments. Immunophilin ligands, cyclosporin A and FK506, have been proved to stimulate synthesis of brain-derived neurotrophic factor (BDNF) and/or glial cell line-derived neurotrophic factor (GDNF) in cultured neurons and astrocytes or in adult rat brain, suggesting a possible use of immunophilin ligands as neuroprotective agents in some neurological disorders. However, the inimunosuppressive activity is disadvantageous for therapeutic use for general disorders. Therefore, we tried to find an active immunophilin ligand without immunpsuppressive activity by focusing the active structure of FK506 and cyclosporin A for binding to immunophilin protein. Dipeptides composed of hydrophobic aminiacid such as Leu-Ile, Pro-Leu or Pro-He that resemble to the active structure of immunosuppressive drugs, and can bind immunophilins. We examined these and their derivatives, and found the Leu-Ile dipeptide as active substances with neurotrophic factor synthesis stimulatory activity and without immunosuppressive activity." As Leu-Ile was considered to bean ideal agent for neuroregeneration, we applied it once a day for 30 days to the rats with spinal cord semi-transection. However, motor activity was not improved even 30 days after the administration. Much more investigation is necessary to evaluate the Leu-Ile activity on the spinal cord nerve regeneration. Particular points to examine are methods for administration and dosage of the drug.

Report

(4 results)
  • 2001 Annual Research Report   Final Research Report Summary
  • 2000 Annual Research Report
  • 1999 Annual Research Report
  • Research Products

    (18 results)

All Other

All Publications (18 results)

  • [Publications] Ohmiya et al.: "Administration of FGF-2 to embryonic mouse brain induces hydrocephalic brain morphology and aberrant differentiation of neurons in the postnatal cerebral cortex"Journal of Neuroscience Research. 65. 228-235 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Ohmiya et al.: "Brain-derived neurotrophic factor alters cell migration of particular progenitor cells in the developing mouse cerebral cortex"Neuroscience Letters. 377. 21-24 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] 古川昭栄, 古川美子: "神経栄養因子の産生調節機構-Ca^<2+>とcAMPシグナルのクロストーク-"組織培養工学. 27. 500-505 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Ohmiya et al.: "Administration of FGF-2 to embryonic mouse brain induces hydrocephal ie brain morphology and aberrant differentiation of neurons in the postnatal cerebral cortex."Journal of Neuroscience Research. 65. 228-235 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Ohmiya et al.: "Brain-derived neurotrophic factor alters cell migration of particular progenitor cells in the developing mouse cerebral cortex."Neuroscience Letters. 377. 21-24 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Furukawra S, and Furukawa Y.: "Mechanisms of neurotrophic factor synthesis-Crosstalk between Ca^<2+> and CAMP signals"Technology for tissue Cultures (in Japanese). 27. 500-505 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Ohmiya et al.: "Administration of FGF-2 to embryonic mouse brain induces hydrocephalic brain morphology and aberrant differentiation of neurons in the postnatal cerebral cortex"Journal of Neuroscience Research. 65. 228-235 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Ohmiya et al.: "Brain-derived neurotrophic factor alters cell migration of particular progenitor cells in the developing mouse cerebral cortex"Neuroscience Letters. 377. 21-24 (2002)

    • Related Report
      2001 Annual Research Report
  • [Publications] 古川昭栄, 古川美子: "神経栄養因子の産生調節機構 -Ca^<2+>とcAMPシグナルのクロストーク-"組織培養工学. 27. 500-505 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] 古川昭栄,古川美子: "神経栄養因子研究の最近の進歩"神経研究進歩. 44巻. 339-349 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] 古川昭栄,古川美子: "神経成長因子(Nerve Growth Factor)"関節外科. 19巻. 110-111 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Mizuma H. et. al.: "Microsphere embolism-induced elevation of nervegrowth factor level and appearance of nervegrowth factor immunoreactivity in activated T-lymphocytes in the rat brain"J. Neurosci. Res.. 55巻. 749-761 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Nitta A. et al.: "Brain-derived neurotrophic factor prevents neuronal cell death induced by corticosterone"J. Neurosci. Res.. 57巻. 227-235 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Fukumitsu H. et al.: "Induction of a physiologically active brain-derived neurotrophic factor in the infant rat brain by peripheral administration of 4-methyleatechol"Neurosci. Lett.. 274巻. 115-118 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Nitta A. et. al.: "4-Methylcatechel increases brain-derived heurotrophic factor content and mRNA expression in cultured brain cells or in vivo of rats"J. Pharmacol. Exp. Ther.. 291巻. 1276-1283 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] 古川昭栄 ら: "神経栄養因子による神経細胞の保護"最新医学. 54巻. 1730-1736 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] 古川美子 ら: "脳と神経-分子神経生物科学入門(金子章造ら編)"共立出版. 363 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] 古川美子 ら: "遺伝子治療開発研究ハンドブック(日本遺伝子治療学会編)"(株)エヌ・ティー・エス. 1061 (1999)

    • Related Report
      1999 Annual Research Report

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Published: 1999-04-01   Modified: 2016-04-21  

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