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Development of compounds to stimulate peripheral nerve regeneration viainduction of nerve growth factor synthesis.

Research Project

Project/Area Number 02454349
Research Category

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

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

Principal Investigator

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

Co-Investigator(Kenkyū-buntansha) NAKAMURA Nobuyuki  Assistant Professor, Department of Orthopedics, Jikei Medical School, 整形外科, 助手 (90198226)
Project Period (FY) 1990 – 1991
Project Status Completed (Fiscal Year 1991)
Budget Amount *help
¥6,700,000 (Direct Cost: ¥6,700,000)
Fiscal Year 1991: ¥3,100,000 (Direct Cost: ¥3,100,000)
Fiscal Year 1990: ¥3,600,000 (Direct Cost: ¥3,600,000)
KeywordsNerve growth factor / Peripheral nerve / Nerve regeneration / Catechol compound / Axonal transport / Ganglion / Sympathetic neuron / Sensory neuron / 再生 / カテコ-ル / 軸索内輸送 / 神経節 / 交感神経 / 知覚神経
Research Abstract

Nerve growth factor (NGF) is a protein that stimulates differentiation and maintains survival of sympathetic nerirons and some sensory neurons in peripheral nervous system. Recent works suggest important roles of NGF during peripheral nerve regeneration. This presents a possibility that NGF may be useful for a therapeutic or a promoting agent for nerve injury. We have already found that some kinds of catechol compounds can stimulate NGF synthesis in vitro. In this research, we aimed to evaluate the compounds with NGF synthesis stimulatory activity as stimulators of NGF synthesis in vivo. For this purpose, we screened various compounds and obtain a series of compounds, alkylcatechols, with potent stimulatory activity of NGF synthesis in vitro. Intraperitoneal administration of one of the alkylcatechols induced an increase in NGF protein and NGF mRNA in the adult rat heart and submaxillary gland. The increase in NGF protein was successively translocated from the sciatic nerve to sensory or sympathetic ganglia. Repetitive administration of an analogue of alkylcatechol caused significant elevations of substance P level in sensory ganglia and tyrosine hydroxylase activity in superior cervical ganglia of infant rats. These observations indicate that alkylcatechols can stimulate NGF synthesis in vivo and that the induced NGF has physiological effects on peripheral neurons. Therefore, we tested one of the alkylcatechols whether it can stimulate peripheral nerve regeneration. Daily injection of methylcatechol for 2 weeks increased the numbers of both myelinated and unmyelinated axons that grew across an 8mm gap after entubational repair of sectioned rat sciatic nerve.

Report

(3 results)
  • 1991 Annual Research Report   Final Research Report Summary
  • 1990 Annual Research Report
  • Research Products

    (31 results)

All Other

All Publications (31 results)

  • [Publications] Shigeno,T.,Mima,T.,Takakura,K.,Graham,D.I.,Kato,G.,Hashimoto,Y.,Furukawa,S.: "Amelioration of delayed neuronal death of the hippocampus by nerve growth factor." J.Neurosci.11. 2914-2919 (1991)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Kawagishi,H.,Ando,M.,Sakamoto,H.,Yoshida,S.,Ojima,F.,Ishiguro,Y.,Ukai,N.,Furukawa,S.: "Hericenones C,D and E,stimulators of nerve growth factor (NGF)-synthesis,from the mushroom Hericium erinaceum." Tetrahed.Lett.,. 32. 4561-4564 (1991)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Hanaoka,Y.,Ohi,T.,Furukawa,Furukawa Y.,Hayashi K.and Matsukura,S.: "Effect of 4-methylcatechol on sciatic nerve growth factor level and motor nerve conduction velocity in experimental diabetic neuropathic process in rats." Exp.Neurol.115. 292-296 (1992)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Ishikawa,R.,Nishikori,K.,Furukawa,Y.,Hayashi,K.,Furukawa,S.: "Lesion-induced reduction of acidic fibroblast growth factor level in the distal part of rat sciatic nerve." Neurosci.Lett.

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Hashimoto,Y.,Kawatsura,H.Shiga,Y.,Furukawa,S.,Shigeno,T.: "Significance of nerve growth factor content levels after forebrain ischemia in gerbil." Neurosci.Lett.

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] 古川 昭栄,河岸 洋和: "神経成長因子の生理的意義とその合成促進物質" 化学と生物. 29. 640-646 (1991)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] 古川 昭栄,古川 美子: "神経伝達物質updateー基礎から臨床まで(中村重信編)" 中外医学社, (1991)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Ohi, T., Furukawa, S., Hayashi, K. and Matsukura, S.: "Ganglioside stimulation of nerve growth factor synthesis in cultured rat schwann cells." Biochem. Int.20. 739-746 (1990)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Shinoda, I., Furukawa, Y. and Furukawa, S.: "Stimulation of nerve growth factor synthesis by propentofylline in cultured mouse astrogical cells." Biochem. Pharmacol.39. 1813-1816 (1990)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Furukawa, Y., Fukazawa, N., Miyama, Y., Hayashi, K. and Furukawa, S.: "Stimulation of 4-alkylcatechol and their diacetylated derivatives on the synthesis of nerve growth factor." Biochem. Pharmacol.40. 2337-2342 (1990)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Furukawa, S., Furukawa, Y.: "Nerve growth factor synthesis and its regulatory mechanisms : An approach to therapeutic induction of nerve growth factor synthesis." Cerebrovasc. Brain Metabol. Rev.2. 328-344 (1990)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Shigeno, T., Mima, T., Takakura, K., Graham, D. I., Kato, G., Hashimoto, Y., Furukawa, S.: "Amelioration of delayed neuronal death of the hippocampus by nerve growth factor." J. Neurosci.11. 2914-2919 (1991)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Kawagishi, H., Ando, M., Sakamoto, H., Yoshida, S., Ojima, F., Ishiguro, Y., Ukai, N., Furukawa, S.: "hericenones C, D and E, stimulators of nerve growth factor (NGF) synthesis, form the mushroom Hericium erinaceus." Tetrahed. Lett.32. 4561-4564 (1991)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Hanaoka, Y., Ohi, T., Furukawa, S., Furukawa Y., Hayashi, K. and Matsukura, S.: "Effect of 4-methylcatechol on sciatic nerve growth factor level and motor nerve conduction velocity in experimental diabetic neuropathic process in rats." Exp. Neurol.115. 292-296 (1992)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Ishikawa, R., Nishikori, K., Furukawa, Y., Hayashi, K., Furukawa, S.: "Lesion-induced reduction of acidic fibroblast growth factor level in the distal part of rat sciatic nerve." Neurosci. Lett.

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Hashimoto, Y., Kawatsura, H., Shiga, Y., Furukawa, S., Shigeno, T.: "Significance of nerve growth factor content levels after forebrain ischemia in gerbil." Neurosci. Lett.

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Shigeno T.,Mima T.,Takakura K.,Graham,D.I.,Kato G.,Hashimoto Y.,Furukawa S.: "Amelioration of delayed neuronal death of the hippocampus by nerve growth factor." J.Neurosci.11. 2914-2919 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] Kawagishi H.,Ando M.,Sakamoto H.,Yoshida S.,Ojima F.,Ishiguro Y.,Ukai N.,Furukawa S.: "Hericenones C,D and E,stimulators of nerve growth factor (NGF)ーsynthesis,from the mushroom Hericium erinaceum." Tetrahed Lett.,. 32. 4561-4564 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] Hanaoka Y.,Ohi T.,Furukawa,Furukawa Y.,Hayashi K.and Matsukura,S.: "Effect of 4ーmethylcatechol on sciatic nerve growth factor level and motor nerve conduction velocity in experimental diabetic neuropathic process in rats." Exp.Neurol.115. 292-296 (1992)

    • Related Report
      1991 Annual Research Report
  • [Publications] Ishikawa R.,Nishikori K.,Furukawa Y.,Hayashi K.,Furukawa S.: "Lesionーinduced reduction of acidic fibroblast growth factor level in the distal part of rat sciatic nerve." Neurosci.Lett.

    • Related Report
      1991 Annual Research Report
  • [Publications] Hashimoto Y.,Kawatsura H.,Shiga Y.,Furukawa S.,Shigeno T.: "Significance of nerve growth factor content levels after forebrain ischemia in gerbil." Neurosci.Lett.

    • Related Report
      1991 Annual Research Report
  • [Publications] 古川 昭栄、河岸 洋和: "神経成長因子の生理的意義とその合成促進物質" 化学と生物. 29. 640-646 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] 古川 昭栄、古川 美子(中村 重信編): "神経伝達物質updateー基礎から臨床まで" 中外医学社, (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] Furukawa Y.,Fukazawa N.,Miyama Y.,Hayashi K.,Furukawa S.: "Stimulation of 4ーalkylcatechol and their diacetylated derivatives on the synthesis of nerve growth factor." Biochem.pharmacol.40. 2337-2342 (1990)

    • Related Report
      1990 Annual Research Report
  • [Publications] Furukawa S.,Furukawa Y.: "Nerve growth factor synthesis and its regulatory mechanisms:An approach to therapeutic induction of nerve growth factor synthesis." Cerebrovasc.Brain Metabol.Rev.2. 328-344 (1990)

    • Related Report
      1990 Annual Research Report
  • [Publications] Shinoda I.,Furukawa Y.,Furukawa S.: "Stimulation of nerve growth factor synthesis by propentofylline in cultured mouse astroglial cells." Biochem.Pharmacol.39. 1813-1816 (1990)

    • Related Report
      1990 Annual Research Report
  • [Publications] Ikegami R.,Furukawa Y.,Kaechi K.,Hayashi K.,Furukawa S.: "Effects of catecholamines and 4ーmethylcatechol on the synthesis and secretion of nerve growth factor by rat sciatic nerve segments in culture." Biomed.Res.11. 61-65 (1990)

    • Related Report
      1990 Annual Research Report
  • [Publications] 古川 昭栄、古川 美子、林 恭三: "神経成長因子(NGF)とアストロサイト" 神経研究の進歩. 34. 526-538 (1990)

    • Related Report
      1990 Annual Research Report
  • [Publications] 西尾 健資、古川 昭栄: "大脳コリン系とNGF" Dementia. 209-219 (1990)

    • Related Report
      1990 Annual Research Report
  • [Publications] 古川 美子、古川 昭栄、林 恭三: "現代化学増刊号18 サイトカイン(神経成長因子)" 東京化学同人, 169-182 (1990)

    • Related Report
      1990 Annual Research Report
  • [Publications] 古川 昭栄、古川 美子: "老年期痴呆ー神経組織障害の修復ー分担執筆" 科学評論社, 62-79 (1990)

    • Related Report
      1990 Annual Research Report

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Published: 1990-04-01   Modified: 2016-04-21  

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