| Project/Area Number |
05680691
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| Research Category |
Grant-in-Aid for General Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Research Field |
Neurochemistry/Neuropharmacology
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| Research Institution | National Institute of Neuroscience |
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Principal Investigator |
KOHSAKA Shinichi (1994) National Institute of Neuroscience, Dep.of Neurochemistry, Director, 神経研究所・代謝研究部, 部長 (50112686)
中嶋 一行 (1993) 国立精神・神経センター, 神経研究所・代謝研究部, 室長 (50175494)
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| Co-Investigator(Kenkyū-buntansha) |
IMAI Yoshinori National Institute of Neuroscience, Dep.of Neurochemistry, Visiting scientist, 神経センター・神経研究所・代謝研究部, 併任研究員
NAKAJIMA Kazuyuki National Institute of Neuroscience, Dep.of Neurochemistry, Section chief, 神経センター・神経研究所・代謝研究部, 室長 (50175494)
高坂 新一 , 部長 (50112686)
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| Project Period (FY) |
1993 – 1994
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| Project Status |
Completed (Fiscal Year 1994)
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| Budget Amount *help |
¥1,900,000 (Direct Cost: ¥1,900,000)
Fiscal Year 1994: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 1993: ¥1,000,000 (Direct Cost: ¥1,000,000)
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| Keywords | Microglia / Neurotrophic factor / Neuron / Protease / Plasminogen / ミクログリア、 / 神経栄養因子、 / ニューロン、 / プロテアーゼ、 / プラスミノーゲン、 |
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| Research Abstract |
Little has been known about the intercellular interaction between neuron and microglia in the brain. We therefore focused on the interaction of these cell types using in vitro system. In particular, the functions of microglia on the neuronal growth and neuronal function were aimed. We planed to survey microglia-derived neurotrophic factors and to identify them and further to resolve the molecular mechanism of neurotrophic effects.
At the first year, we detected neurotrophic activity on the rat neocortical neuron and mesencephalic neuron in the microglial conditioned medium. Apart from the findings of these neurotrophic effects, three kinds of proteases such as elastase, urokinase type plasminogen activator (uPA) and plasminogen were identified. The relationship between these proteases and neurotrophic effects were examined by adding these proteases into the cultured neurons. Of these proteases, plasminogen showed the neurotrophic effects such as the enhancement of neurite extension and dopamine uptake. These results suggested that the neurotrophic effects of plasminogen would be exerted through a certain signal transduction cascade by binding to the specific receptor protein on the neuronal surface.
In the second year, we found a 45kDa protein which can bind plasminogen on the neuronal plasma membrane, and focused on this protein as a candidate of plasminogen-receptor. As a result of amino acid sequence analysis, the purified protein turned out as rat alpha-enolase. This result was confirmed by immunological reactivity of anti rat alpha-enolase antibody. Immunocytochemical study also showed that some alpha-enolase exist on the neuronal plasma membrane. Whether alpha-enolase is associated with a signal transduction or not is currently under investigation.
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