| Project/Area Number |
13557222
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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 | 展開研究 |
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| Research Field |
応用薬理学・医療系薬学
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| Research Institution | Osaka University |
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Principal Investigator |
KOYAMA Yutaka Osaka Univ., Grad. Sch. of Pharmaceutical Sci., Associate Prof., 薬学研究科, 助教授 (00215435)
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| Co-Investigator(Kenkyū-buntansha) |
BABA Akemichi Osaka Univ., Grad.Sch.of Pharmaceutical Sci., Prof, 薬学研究科, 教授 (70107100)
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| Project Period (FY) |
2001 – 2003
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| Project Status |
Completed (Fiscal Year 2003)
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| Budget Amount *help |
¥8,300,000 (Direct Cost: ¥8,300,000)
Fiscal Year 2003: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 2002: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 2001: ¥6,300,000 (Direct Cost: ¥6,300,000)
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| Keywords | Glia cells / Astrocyte / GDNF / Neurotrophic drugs / BDNF / neurotrophic factors / 海馬 / グルタミン酸 / 脳浮腫 / Na / Ca交換輸送 |
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| Research Abstract |
Effects of Endothelin Receptor Agonists on Neurotrophic Factor Production in cultured Astrocytes: Re-generation of nervous systems after injury is supported by neurotrophic substances produced by astrocytes. In this study, we examined effects of a receptor agonist of endothelin-1 (ET-1), which increased in damages brain, on neurotrophic factor production in astrocytes. ET-1 stimulated expressions of glial cell line-derived neurotrophic factor (GDNF) and brain-derived neurotrophic factor (BDNF) in cultured astrocytes. Intracerebroventircular administration of an ET receptor agonist Into rat brain increases both mRNA and protein levels of GDNF in hippocampus. BDNF expression in caudate putamen and cerebrum also increased by the ET agonist. Cultured astrocytes had exon 3 and exon 4-containing BDNF transcripts, but not exon 1 and exon 2 transcripts. Treatment with ET-1 increased both exon 3 and exon 4-containing BDNF transcripts. Examinations on ET-induced astrocytic BDNF transcription showed that the exon 3 of DNF gene were induced by ERK and CREB-mediated mechanisms. The exon 4 BDNF gene was shown to be mediated by C/EBPβ-mediated mechanisms. These results suggest that ET receptors are possible target of neurotrophic drugs.
Mechanisms of novel neurotrophic drugs: T-588, a navel drug showing nouroprotective actions, caused Erk activation in rat hippocampus. Also, we found FK960, which have cognitive enhancing actions in animal models, stimulated GDNF production in rat cultured astrocytes. These actions of novel neurotrophic drugs may underlie their phsrmacological actions.
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