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Significance of microglia derived plasmin-generating proteases in the nervous system

Research Project

Project/Area Number 07680864
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Neurochemistry/Neuropharmacology
Research InstitutionNational Institute of Neuroscience

Principal Investigator

NAKAJIMA Kazuyuki  National Institute of Neuroscience, Dept. of Neurochemistry, Section Chief, 神経研究所・代謝研究部, 室長 (50175494)

Co-Investigator(Kenkyū-buntansha) IMAI Yoshinori  National Institute of Neuroscience, Dept. of Neurochemistry, Section Chief, 神経センター神経研究所・代謝研究部, 室長 (20270689)
KOHSAKA Shinichi  National Institute of Neuroscience, Dept. of Neurochemistry, Director, 神経センター神経研究所・代謝研究部, 部長 (50112686)
Project Period (FY) 1995 – 1996
Project Status Completed (Fiscal Year 1996)
Budget Amount *help
¥2,100,000 (Direct Cost: ¥2,100,000)
Fiscal Year 1996: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 1995: ¥1,000,000 (Direct Cost: ¥1,000,000)
Keywordsmicroglia / plasminogen / plasminogen activator
Research Abstract

The aim of this study was to study (1) action mechanism of plasminogen in the neuron, (2) production of microglia-derived proteases in the brain, (3) regulatory factor of secretory proteases from microglia.
(1) We studied the action of plasminogen and prodiction of inositol tri-phosphate (IP3) or protein-phosphorylations in the cultured neuron derived from neonatal rat brain, and found taht plasminogen induces a transiient increase of IP3 and causes a tyrosine- phosphorylation in a certain protein(>100kDa) of cultured neuron. However, since, in the latter case, the degree of phophorylation was very low and delicate, it is necessary to be confirmed by trustworthy study.
(2) Using the transection model of rat facial nerve, we showed taht plasminogen activator activity was transiently induced in axotomized facial nucleus. The plasminogen activator was characterized and identified as urokinase type plasminogen activator (uPA) from the results of response to the uPA inhibitor, amiloride, and of the molecular weight. The cell producing uPA in the facial nucleus was sugested to be microglia. Plasminogen was also suggested to increase in axotomized facial nucleus.
(3) We surveyed the factors which elevate the amounts of plasminogen and/or plasminogen activator in microglia, and found that neurotrophin has an ability to promote the secretion of plasminogen and uPA.Nerve growth factor, brain-derived neurotrophic factor, neurotrophon-3 and neurotrophin-4/5 were comparable for the increasing effect. The neurotrophin had a capacity to decrease the release of nitric oxide from microglia. The analysis of specific receptor for the neurotrophins in cultured microglia revealed the expression of trk A,trk B and trk C at both mRNA and protein level.

Report

(3 results)
  • 1996 Annual Research Report   Final Research Report Summary
  • 1995 Annual Research Report
  • Research Products

    (15 results)

All Other

All Publications (15 results)

  • [Publications] Nakajima K: "Induction of urokinase-type plasminogen activator in rat facial nucleus by axotomy of the facial nerve" Journal of Neurochemistry. 66. 2500-2505 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Hamanoue M: "Neurotrophic effect of hepatocyte growth factor on CNS neurons in vitro" Journal of Neuroscience Research. 43. 554-564 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] 中嶋一行: "グリア細胞と神経栄養因子:最近の進歩" 神経精神薬理. 18. 765-770 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Nakajima K: "Topical issues in microglia research" Goh Bros (Enterprise Humanities Press), 16 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Hamanoue, M., Takemonot, N., Matsumoto, K., Nakamura, T., Nakajima, K.and Kohsaka, S.: "Neurotrophic effect of hepatocyte growth factor on central nervous system neurons in vitro" J.Neurosci. Res.43. 554-564 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Nakajima, K., Reddington, M., Kohsaka, S.and Kreutzberg, GW.: "Induction of urokinase-type plasminogen activator in rat facial nucleus by axotomy of the facial nerve" J.Neurochem.66. 2500-2505 (1966)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Nakajima, K and Kohsaka, S.: Functional implications of microglia-derived secretory proteases : in Topical issues in microglia research. Enterprise Humanities Press (Goh Bros), 203-218 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Hamanoue M: "Neurotrophic effect of hepatocyte growth factor on CNS neurons in vitro" Journal of Neuroscience Research. 43. 554-564 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Nakajima K: "Induction of urokinase-type plasminogen activator in rat facial nucleus by axotomy of the facial merve" Journal of Neurochemistry. 66. 2500-2505 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] 中嶋一行: "グリア細胞と神経栄養因子:最近の進歩" 神経精神薬理. 18. 765-770 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Nakajima K: "Topical issues in microglia research" Goh Bros (Enterprise Humanities Press), 16 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] 中嶋一行: "グリア細胞由来神経栄養因子" Clinical Neuroscience. 13. 839-842 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] 中嶋一行: "ミクログリアと病巣修復" 神経研究の進歩. 39. 966-973 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Nakajima K: "Induction of urokinase-type plasminogen activator in rat facial nucleus by axotomy of the facial nerve" Journal of Neurochemistry. (in press). (1996)

    • Related Report
      1995 Annual Research Report
  • [Publications] Hamanoue M: "Neurotrophic effect of hepatocyte growth factor on CNS neurons in vitro" Journal of Neuroscience Research. (in press). (1996)

    • Related Report
      1995 Annual Research Report

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Published: 1995-04-01   Modified: 2016-04-21  

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