| Project/Area Number |
08457637
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
応用薬理学・医療系薬学
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| Research Institution | Kagoshima University |
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Principal Investigator |
FUKUDA Takeo Faculty of Medicine, Kagoshima University, Professor, 医学部, 教授 (70038694)
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| Co-Investigator(Kenkyū-buntansha) |
IWATA Shin-ichi Faculty of Medicine, Kagoshima University, Research Associate, 医学部, 助手 (60253861)
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| Project Period (FY) |
1996 – 1998
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| Project Status |
Completed (Fiscal Year 1998)
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| Budget Amount *help |
¥5,500,000 (Direct Cost: ¥5,500,000)
Fiscal Year 1998: ¥600,000 (Direct Cost: ¥600,000)
Fiscal Year 1997: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 1996: ¥4,100,000 (Direct Cost: ¥4,100,000)
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| Keywords | neuromodulin / GAP-43 / in situ hybiridization / dopamine neuron / 6-hydroxydopamine / tyrosine hydroxylase / down regulation / mRNA / in situ ハイブリダイゼーション / ドパミン / 線条体 / 黒質 / sprouting / NM / 6-OHDA |
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| Research Abstract |
Neuromodulin (NM)(GAP-43) is neuron-specific protein enriched in the growth cone. It has been reported to be related with axonal regeneration though its function is still unknown. In this study, we examined the alteration of NM after the destruction of dopaminergic terminals, and tried to elucidate the function of NM as to the capacity of regeneration of dopaminergic neurons ; furthermore, reason why dopaminergic neurons are damaged in Parkinson's disease. Results obtained in the study are as follows ;
1. the nigrostriatal dopaminergic terminals possessed relatively a great portion of all NM in the striatum than synapsin I, synaptotagmin, syntaxin, synaptobrevin, or SNAP-25.
2. small changes in NM contents in the nigrostriatal terminals were masked by NM in the corticostriatal terminals, which is the most dominant terminals in the striatum.
3. Although a high dose of 6-hydroxydopamine injected in the striatum gradually degenerated dopaminergic cell bodies in addition to their terminals, with small dose of 6-hydroxydopamine, dopaminergic terminals can regenerate after the initial destruction of their terminals.
4. the number of NM mRNA positive neurons and that of tyrosine hydroxylase (TH) mRNA positive neurons decreased though contents of NM and TH gradually restored.
These results suggest that the alteration of NM content is small even when dopaminergic terminals regenerate, and that the downregulation of NM mRNA and TH mRNA in the dopaminergic neurons may be a reason of specific degeneration of dopaminergic neurons in Parkinson's disease. We arc planning to detect dopaminergic axons in the striatum with antiNM antibody and antiTH antibody using a confocal laser microscope and to find the alteration of NM specific to the nigrostriatal dopaminergic terminals. Moreover, quantification of house-keeping mRNAs should be investigated in order to elucidate whether the downregulation of NM mRNA and THmRNA are confined to these mRNAs.
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