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Development investigation for enhancement of regeneration and amelioration of function of the damaged peripheral nerves by medical regulation of neurotrophin synthesis.

Research Project

Project/Area Number 05557067
Research Category

Grant-in-Aid for Developmental Scientific Research (B)

Allocation TypeSingle-year Grants
Research Field Orthopaedic surgery
Research InstitutionGifu Pharmaceutical University

Principal Investigator

FURUKAWA Shoei  Gifu Pharmaceutical University, Laboratory of Molecular Biology, Professor, 薬学部, 教授 (90159129)

Co-Investigator(Kenkyū-buntansha) KAWAGISHI Hirokazu  Shizuoka University, Faculty of Agriculture, Associate Professor, 農学部, 助教授 (70183283)
OHI Takekazu  Miyazaki Medical College, The Third Department of Internal Medicine, Associate P, 医学部, 助教授 (80135615)
FURUKAWA Yoshiko  Aichi Bunkyo Woman's College, Professor, 教授 (20219108)
Project Period (FY) 1993 – 1995
Project Status Completed (Fiscal Year 1995)
Budget Amount *help
¥19,600,000 (Direct Cost: ¥19,600,000)
Fiscal Year 1995: ¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 1994: ¥3,800,000 (Direct Cost: ¥3,800,000)
Fiscal Year 1993: ¥12,300,000 (Direct Cost: ¥12,300,000)
KeywordsNEUROTROPHIC FACTORS / NEUROTROPHIN / NERVE GROWTH FACTOR / BRAIN-DERIVED NEUROTROPHIC FACTOR / NEUROTROPHIN-3 / 4 METHYLCATECHOL / PERIPHERAL NERVES / NERVE REGENERATION / NGF / BDNF / NT-3
Research Abstract

(1) EFFECTIVE IMPROVEMENT ON NEURONAL DYSFUNCTION BY ADMINISTRATION OF 4-METHYLCATECHOL (4-MC) IN DIABETIC OR ACRYLAMIDE-INDUCED PERIPHERAL NEUROPATHY.
Streptozotocin (STZ) -induced diabetic rats showed a reduction in motor nerve conduction velocity (MNCV), myelinated axon diameter, and nerve growth factor (NGF) content in the sciatic nerve. 4-MC treatment started 4 weeks after the STZ injection resulted in improvements on all of these damages in diabetic rats. In acrylamide (ACR) -induced neuropathy, when ACR and 4-MC were coadministered intraperitoneallys, improved clinical signs, and more NGF content in the sciatic nerves, faster MNCV,and greater myelinated fiber density than in rats given ACR alone were found. These findings suggest that a decreased NGF level may be involved in the pathogenesis of diabetic and ACR-induced neuropathies and that 4-MC treatment could be a useful therapy.
(2) PREPARATION OF ANTIBODIES SPECIFICALLY RECOGNIZE BRAIN-DERIVED NEUROTROPHIC FACTOR (BDNF) AND NEUROTROPHIN-3 (NT-3).
Quantitative methods to detect respective neurotrophins are necessary to evaluate theirroles in regeneration and functional repair of perigheral nerves. We succeeded to raise antibodies in chicken specifically recognize BDNF or NT-3. Two-site enzyme immunoassaies using these antibodies could detect BDNF and/or NT-3 as low as a concentration of a few pg/ml.
(3) REGULATION OF BDNF EXPRESSION IN NEURONS CULTURED FROM CHICK DORSAL ROOT GANGLIA (DGR).
Recent reports localize BDNF mRNA in the neurons cultured from chick embryo DRG,which are known responsive to BDNF.To estimate physiological roles of BDNF expression in the DRG neurons, we investigated changes of BDHF-like immunoreactivity during depolarization, and found that it caused a transient decrease in expression of BDNF protein. This suggests that stimuli-transmission followd by depolarization suppresses BDNF synthesis in DRG neurons during maturation of peripheral sensory system.

Report

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

    (18 results)

All Other

All Publications (18 results)

  • [Publications] Kaechi,K. et ai.: "4-Methylcatechol,an inducer of NGF synthesis,enhances peripheral nerve regeneration across nerve gaps." J. Pharmacol. Exp. Ther.272. 1300-1304 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Awatsuji. H. et al.: "Interferones suppress nerve growth factor synthesis as a result of interference of cell growth in astrocytes cultured from neonatal mouse brain." J. Neurochem.64. 1476-1482 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Saita,K. et al.: "Effects of 4-methylcatechol,a stimulator of endogenous nerve growth factor synthesis,on experimental acrylamide neuropathy in rats." Neurotoxicol.16. 403-412 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Kojima,H. et al.: "Construction and characterization of adenoviral vector expressing biologically active brain-derived neurotrophic factor." Biochem. Biophys. Res. Commum.212. 712-717 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Saita,K. et al.: "A catechol derivative (4-methylcatechol) accelerates the recovery from experimental acrylamide-induced neuropathy." J. Pharm. Exp. Ther.276. 231-237 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] 古川昭栄: "ニューロトロフィンと神経病巣修復." 神経研究の進歩. 39. 957-965 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Kaechi,K.et al.: "4-Methylcatechol,an inducer of NGF synthesis,enhances poripheral nerve regeneration across nerve gaps." J.Pharmacol.Exp.Ther.272. 1300-1304 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Awatsuji,H.et al.: "Interferones suppress nerve growth factor synthesis as a result of interference of cell growth in astrocytes cultured from neonatal mouse brain." J.Neurochem.64. 1476-1482 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Saita,K.et al.: "Effects of 4-methylcatechol,a stimulator of endogenous nerve growth factor synthesis,on experimental acrylamide neuropathy in rats." Neurotoxicol.16. 403-412 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Kojima,H.et al.: "Construction and characterization of adenoviral vector expressing biologically active brain-derived neurotrophic factor." Biochem.Biophys.Res.Commun.212. 712-717 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Saita,K.et al.: "A catechol derivative(4-methylcatechol) accelerates the recovery from experimental acrylamide-induced neuropathy." J.Pharm.Exp.Ther.276. 231-237 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] 古川昭栄: "ニューロトロフィンと神経病巣修復." 神経研究の進歩. 39. 957-965 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] 古川昭栄: "NGF合成誘導による末梢神経再生促進" 末梢神経. 3. 103-109 (1993)

    • Related Report
      1994 Annual Research Report
  • [Publications] 古川昭栄、古川美子: "アストロサイトにおける神経成長因子合成-その生理的意義と調節機構-21GC02:細胞" 25. 10-14 (1993)

    • Related Report
      1994 Annual Research Report
  • [Publications] 古川美子、古川昭栄: "痴呆と神経成長因子" 老年期痴呆. 7. 51-60 (1993)

    • Related Report
      1994 Annual Research Report
  • [Publications] Furukawa,Y.et al.: "Alkylcatechols regulate NGF gene expression in astroglial cells viaboth protein kinase C-and cAMP-independent mechanisms." J.Neursci.Res.35. 522-529 (1993)

    • Related Report
      1994 Annual Research Report
  • [Publications] Ueyama,T.et al.: "Production of nerve growth factor by cultured vascular smooth muscle cells from spontaneously hypertensive and Wistar-Kyoto rats." J.Hypertension. 11. 1061-1065 (1993)

    • Related Report
      1994 Annual Research Report
  • [Publications] Kaechi,K.et al.: "Pharmacological induction of physiologically active nerve growth factor in rat peripheral nervors system." J.Pharmacol.Exp.Ther.264. 321-326 (1993)

    • Related Report
      1994 Annual Research Report

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Published: 1993-04-01   Modified: 2016-04-21  

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