| Project/Area Number |
20390023
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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 |
Biological pharmacy
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| Research Institution | University of Toyama |
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Principal Investigator |
MASAAKI Tsuda University of Toyama, 大学院・医学薬学研究部(薬学), 教授 (80132736)
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| Co-Investigator(Kenkyū-buntansha) |
AKIKO Tabuchi 富山大学, 大学院・医学薬学研究部(薬学), 准教授 (40303234)
MAMORU Fukuchi 富山大学, 大学院・医学薬学研究部(薬学), 助教 (40432108)
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| Project Period (FY) |
2008 – 2010
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| Project Status |
Completed (Fiscal Year 2010)
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| Budget Amount *help |
¥18,980,000 (Direct Cost: ¥14,600,000、Indirect Cost: ¥4,380,000)
Fiscal Year 2010: ¥6,110,000 (Direct Cost: ¥4,700,000、Indirect Cost: ¥1,410,000)
Fiscal Year 2009: ¥5,850,000 (Direct Cost: ¥4,500,000、Indirect Cost: ¥1,350,000)
Fiscal Year 2008: ¥7,020,000 (Direct Cost: ¥5,400,000、Indirect Cost: ¥1,620,000)
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| Keywords | 遺伝子発現 / シナプス / BDNF / PACAP / CREB / MKL / GPCR / Arc / MAL/MKL / TORC / カルシウム / MAL / アクチン / SRF |
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| Research Abstract |
Since G protein-coupled receptors (GPCRs) potentiate the activity of the N-methyl-D-aspartate receptor (NMDA-R), we comprehensively investigated gene expression induced by the stimulation of GPCRs in culture. Potentiation of NMDA-R mediated by the activation of PAC1, a GPCR, with PACAP immediately activated a limited number of genes upon Ca^<2+> signals. The mRNA expression of the brain-derived neurotrophic factor exon IV-IX (Bdnf-eIV) is totally controlled by Ca^<2+>/calcineurin, leading to the CRE/CREB-dependent transcription. Stimulation of NMDA-R under the activation of PAC1 synergistically increased Bdnf-eIV mRNA expression through the selective activation of calcineurin, leading to translocation of TORC1 to nucleus and activation of CREB-KID domain. The Ca^<2+>/calcineurin-dependent mRNA expression was also induced by direct stimulation of PKA or PKC pathway and, furthermore, by that of the dopamine D1 or β-adrenergic receptor. Thus, the potentiation of NMDA-R activity mediated by GPCR induces activity-dependent gene expression through calcineurin pathway, possibly regardless of the type of neurotransmission.
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