| Project/Area Number |
05680674
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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 | Osaka University |
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Principal Investigator |
IKEUCHI Toshihiko Osaka University, Institute for Protein Research, Associate Professor, たんぱく質研究所, 助教授 (20093362)
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| Co-Investigator(Kenkyū-buntansha) |
HATANAKA Hiroshi Osaka University, Institute for Protein Research, Professor, たんぱく質研究所, 教授 (60208519)
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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 |
¥2,100,000 (Direct Cost: ¥2,100,000)
Fiscal Year 1994: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 1993: ¥1,300,000 (Direct Cost: ¥1,300,000)
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| Keywords | Nerve Growth Factor / NGF Receptor / RT-PCR Method / Differentiation of Neurons / Cultured Neuronal Cell / Cholinergic Neurons |
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| Research Abstract |
Using a quantitative RT-PCR,we studied the regulation of trkA mRNA expression in serum-free, cultured basal forebain neurons from 17-day fetal rats. Besides increasing ChAT activities, NGF strikingly induced trkA gene expression in a time- and NGF concentration-dependent manner. Therefore, NGF might play a critical role in trkA gene expression during the development of basal forebrain cholinergic neurons. Furthermore, to investigate whether this up-regulation is connected with the trophic effects on basal forebrain cholinergic neurons, we examined the effects of some other neurotrophic agents (BDNF,NT-3, bFGF,CNTF and 40 mM KC1) upon ChAT activity and trkA gene expression. Some neurotrophic factors increased ChAT activities to the same degree as NGF,whereas they did not stimulate trkA mRNA expression so potently. NT-3 plus K252b promotes the tyrosine phosphorylation of TrkA in PC12 cells and increases ChAT activity in cultured basal forebrain cholinergic neurons like NGF.We found that NT-3 plus K252b up-regulated the level of trkA mRNA.These results suggested that the expression of trkA mRNA is regulated directly by its specific ligand NGF,rather than by neurotrophic effects upon basal forebrain cholinergic neurons and that the up-regulation is connected to a molecular event initiated by the binding of NGF to the TrkA receptor.
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