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Stimulation of spinal cord regeneration by stimulator of NGF synthesis

Research Project

Project/Area Number 03454368
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 Yoshiko  Gifu Pharmaceurical Univ., Dept. of Pharm. Lecturer, 薬学部, 助手 (20219108)

Co-Investigator(Kenkyū-buntansha) HAYASHI Kyozo  Gifu Pharmaceurical Univ., Dept. of Pharm. Prof., 薬学部, 教授 (00029935)
FURUKAWA Shoei  Gifu pharmaceurical Univ., Dept. of Pharm. As. Prof., 薬学部, 助教授 (90159129)
NAKAMURA Nobuyuki  Jikeikai Med. School of Medicine, Dept. of Med. Lecturer, 医学部, 助手 (90198226)
Project Period (FY) 1991 – 1992
Project Status Completed (Fiscal Year 1992)
Budget Amount *help
¥6,000,000 (Direct Cost: ¥6,000,000)
Fiscal Year 1992: ¥3,200,000 (Direct Cost: ¥3,200,000)
Fiscal Year 1991: ¥2,800,000 (Direct Cost: ¥2,800,000)
Keywordsnerve growth factor / NGF / spinal cord / degeneration of spinal cord / regeneration of nerve / NGF合成促進
Research Abstract

Nerve growth factor (NGF) is a target derived trophic agent which promotes the survival and cellular metabolism of sympathetic neurons, neural crest-derived sensory neurons and basal forebrain cholinergic neurons. It is known that the proximal and/or distal stumps of severed nerve in the peripheral nervous system have an increase in NGF levels, and their responses as degeneration or neuronal cell death can be prevented with systemically administered exogenous NGF. The atrophy of cholinergic neurons in aged brain can be prevented with intraventricular administration of NGF. Although the spinal cord injury results the serious functional deficit, the specific function of NGF in the spinal cord is unknown.
With the aim of gaining insight into the specific function of NGF in the spinal cord during degeneration/regeneration, we used the model of spinal cord transection, and determined temporal changes of NGF and NGFmRNA levels after the transection. As NGF displays a broad distribution in each segment (200 to 300 pg/g wet tissue) of spinal cord in young adult rat, we established the model of spinal cord transection (T-6) on 10-week-old Wistar rat. In the beginning at 2 days after transection (2d), NGF displays a significant increase at the rostral stump of transection site (p<0.01). Then, at both (rostral and caudal) stumps, the level of NGF significantly increase 2 to 3-folds at 4d, 2 to 4-folds at 6d. The significant increases of NGF at both stumps are detected from 4d through 8d, and those at the rostral stump are detected from 2d through 21d. At the both stumps, the expression of NGF mRNA increase at 1d,then gradually decrease from 2d though 8d. The increase of NGF and NGFmRNA levels in the both stumps are stimulated by the administration of catechol compound, which is known to be a stimulator of NGF synthesis in cell culture or peripheral nervous system. These results suggest that NGF may play an important role in the regeneration of spinal cord.

Report

(3 results)
  • 1992 Annual Research Report   Final Research Report Summary
  • 1991 Annual Research Report
  • Research Products

    (34 results)

All Other

All Publications (34 results)

  • [Publications] Murase,K.,Furukawa,Y.,Iwane,M.and Hayashi,K.: "Development of sensitive enzyme immunoassay for human nerve growth factor." Biochem.Int.25. 29-34 (1991)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] Hanaoka,Y.,Ohi,T.,Furukawa,S.,Furukawa,Y.,Hayashi,K.,Mastukura,S.: "Effect of 4-methylcatechol on sciatic nerve growth factor livel 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
      1992 Final Research Report Summary
  • [Publications] Murase,K.,Murakami,Y.,Takayanagi,K.Furukawa,Y.Hayashi,K.: "Human fibroblast cells synthesize and secrete nerve growth factor in culture." Biochem.Biophys.Res.Commun.184. 373-379 (1992)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] Kaechi,K.,Furukawa,Y.,Ikegami,R.,Nakamura,N.Hashimoto,Y.,Omae,F.,Hayashi,K.Furukawa,S.: "Pharmacological induction of physiologically active nerve growth factor." J.Pharmacol.Exp.Thr.264. 321-326 (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] Furukawa,Y.,Furukawa,S.Omae,F.,Awatsuji,H.and Hayashi,K.: "Alkylcatechol regulate NGF gene expression in astroglial cells via both protein kinase C- and cAMP-independent mechanisms." J.Neurosci,Res.(1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] Awatsuji,H.,Furukawa,Y.,Hirota,M.,Murakami,Y.,Nii,S.,Furukawa,S.,Hayashi,K.: "Interleukin-4 and -5 as modulators of nerve growth factor synthesis/secretion in astrocytes." J.Neurosci,Res.(1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1992 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, 309 (1991)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] Yoshiko Furukwa: "Neurotrophic Factors:Taniguchi Symposia on Brain Sciences No.1(Tsukada,Y.& Shooter,E.,eds)" Japan Scientific Societies Press(Tokyo), 243 (1992)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] Murase, K., Furukawa, Y., Iwane, M. and Hayashi, K.: "Development of sensitive enzyme immunoassay for human nerve growth factor." Biochem. Int.25(1). 29-34 (1991)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] Hanaoka, Y., Ohi, T., Furukawa, S., Furukawa, Y., Hayashi, K. and Mastukura, 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
      1992 Final Research Report Summary
  • [Publications] Ishikawa, R., Nishikori, K., Furukawa, Y., Hayashi, K. and Furukawa, S.: "Lesion-induced reduction of acidic fibroblast growth factor level in the distal part of rat sciatic nerve." Neurosci. Lett.135. 113-116 (1992)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] Murase, K., Murakami, Y., Takayanagi, K., Furukawa, Y., and Hayashi, K.: "Human fibroblast cells synthesize and secrete nerve growth factor in culture." Biochem. Biophys. Res. Commun.184(1). 373-379 (1992)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] Nitta, A., Furukawa, Y., Hayashi, K., Hiramatsu, M., Kameyama, T., Hasegawa, T. and Nabeshima, T.: "Denervation of dopaminergic neurons with 6-hydroxydopamine increases nerve growth factor content in rat brain." Neurosci. Lett.144. 152-156 (1992)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] Murase, K., Takeuchi, R., Iwata, E., Furukawa, Y., Furukawa, S. and Hayashi, K.: "Development changes in nerve growth factor level in rat serum." J. Neurosci. Res.33. 282-288 (1992)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] Kaechi, K., Furukawa, Y., Ikegami, R., Nakamura, N., Hashimoto, Y., Omae, F., Hayashi, K. and Furukawa, S.: "Pharmacological induction of physiologically active nerve growth factor." J. Pharmacol. Exp. Thr.264(1). 321-326 (1992)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] Awatsuji, H., Furukawa, Y., Hirota, M., Murakami, Y., Nii, S., Furukawa, S. and Hayashi, K.: "Interleukin-4 and -5 as modulators of nerve growth factor synthesis/secretion in astrocytes." J. Nuerosci. Res.

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] Awatsuji, H., Furukawa, Y., Nakajima M., Furukawa, S. and Hayashi, K.: "Interleukin-2 as a neurotrophic factor for supporting the survival of neurons cultured from various regions of fetal rat brain." J. Neurosci. Res.

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] Furukawa, Y., Furukawa, S., Omae, F., Awatsuji, H. and Hayashi, K.: "Alkylcatechol regulate NGF gene expression in astroglial cells via both protein kinase C- and cAMP-independent mechanisms." J. Neurosci. Res.

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] Yoshiko Furukawa: "Regulation of nerve growth factor synthesis by catechol derivatives." Neurotrophic Factors (Tsukada, Y. & Shooter, E. eds) Japan Scientific Societies Press(Tokyo). 61-72 (1992)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] Kaechi,K.,Furukawa,Y.,Ikegami,R.,Nakamura,N.,Hashimoto,Y.,Omae,F.,Hayashi,K.,Furukawa,S.: "Pharmacological induction of physiologically active nerve growth factor." J.Pharmacol.Exp.Thr.264. 321-326 (1993)

    • Related Report
      1992 Annual Research Report
  • [Publications] Awatsuji,H.,Furukawa,Y.,Hirota,M.,Murakami,Y.,Nii,S.,Furukawa,S.,Hayashi,K.: "Interleukin-4 and-5 as modulators of nerve growth factor synthesis/secretion in astrocytes." J.Neurosci.Res.

    • Related Report
      1992 Annual Research Report
  • [Publications] Awatsuji,H.,Furukawa,Y.,Nakajima,M.,Furukawa,S.,Hayashi,K.: "Interleukin-2 as a neurotrophic factor for supporting the survival of neurons cultured from various regions of fetal rat brain." J.Neurosci.Res.

    • Related Report
      1992 Annual Research Report
  • [Publications] Furukawa,Y.,Furukawa,S.,omae,F.,Awatsuji,H.and Hayashi,K.: "Alkylcatechol regulate NGF gene expression in astroglial cells via both protein kinase C-and cAMP-independent mechanisms." J.Neurosci.Res.

    • Related Report
      1992 Annual Research Report
  • [Publications] 古川 美子、古川 昭栄: "医学と医療の最前線ーーNerve growth factor" 日本内科学会雑誌. 81. 1711-1718 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] 古川 美子: "神経成長因子(NGF)" 日本臨床. 50. 1910-1917 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] Yoshiko Furukawa: "Neurotrophic Factors:Taniguchi Symposia on Brain Sciences No.1 (Tsukada,Y.& Shooter,E.,eds)" Japan Scientific Societies Press(Tokyo), 243 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] 古川 美子、古川 昭栄: "ニューロサイエンス講座第2巻、神経伝達物質受容体ー構造と機能、(佐藤公道、野村靖幸編)" 広川書店,

    • Related Report
      1992 Annual Research Report
  • [Publications] Murase K.,Furukawa Y.,Iwane M. and Hayashi K.: "Development of sensitive enzyme immunoassay for human nerve growth factor." Biochem.Int.,. 25. 29-34 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] Hanaoka Y.,Ohi T.,Furukawa S. 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. and 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] Furukawa Y.,Furukawa S.,Omae F.,Awatsuji H. and Hayashi K.:"Role of protein kinase C in regulatory mechanism of nerve growth factor syntesis." J.Neurosci.Res.

    • Related Report
      1991 Annual Research Report
  • [Publications] 古川 昭栄、古川 美子: "神経成長因子" 神経精神薬理. 13. 771-784 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] 古川 美子: "Nerve Growth Factor" 内科. 67. 743-745 (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, 309 (1991)

    • Related Report
      1991 Annual Research Report

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Published: 1991-04-01   Modified: 2016-04-21  

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