| Project/Area Number |
11672164
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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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 | TOYAMA MEDICAL AND PHARMACEUTICAL UNIVERSITY |
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Principal Investigator |
TSUDA Masaaki Toyama medical and Pharmaceutical University Pharmaceutical Science Professor, 薬学部, 教授 (80132736)
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| Co-Investigator(Kenkyū-buntansha) |
TABUCHI Akiko Toyama medical and Pharmaceutical University Pharmaceutical Science Assistant Researcher, 薬学部, 助手 (40303234)
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| Project Period (FY) |
1999 – 2000
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| Project Status |
Completed (Fiscal Year 2000)
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| Budget Amount *help |
¥3,200,000 (Direct Cost: ¥3,200,000)
Fiscal Year 2000: ¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 1999: ¥1,800,000 (Direct Cost: ¥1,800,000)
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| Keywords | BDNF / PACAP / apoptosis / Calcium / Transcription / CREB / synapse / MAPK / ERK / ニューロン / アコニターゼ / ミトコンドリア / c-jun |
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| Research Abstract |
In this study, we investigated molecular mechanisms for regulation of calcium (Ca^<2+>) signal-dependent gene expression which is responsible for an activation of neuronal cells. We are now focusing on the transcription regulation of neurotrophic factor genes, especially brain-derived neurotrphic factor (BDNF) gene.
1. Analysis of the Ca^<2+> signal-resposiveness of BDNF gene promoters
(1) Differential activation of BDNF gene promoters : Against the Ca^<2+>-influx into neurons through L-type voltage-dependent Ca^<2+> channels (L-VDCC) and N-methyl-D-aspartate receptors (NMDA-R), the BDNF gene promoter I (BDNF-PI) mainly responded to tha Ca^<2+> influx through L-VDCC and the BDNF-PIII to both the Ca^<2+> influxes through L-VDCC and NMDA-R.
(2) Identification of Ca^<2+>-responsive element of BDNF-PI : The CRE located between -90〜-80 nucleotides upstream of transcription initiatiation site was largely responsible for the Ca^<2+> signal-induced activation of BDNF-PI.
2. Analysis of Ca^<2+>-responsve transcription of PACAP gene promoter : The two distinct regions located upstream and downstream, respectively, of initiation site of pituitary adenylate cyclase activating polypeptide (PACAP) were responsible for its Ca^<2+> signal responsiveness.
3. Intracellular siganal pathways transmitted by PACAP : Endogenously synthesized PACAP was effective to survive neuronal cells in culture. Activation of MAP kinase/ERK was effective to survive neurons and the signallings evoked via MAPK/ERK are transmitted to mitochondria and nucleus.
4. Effect of exogenous BDNF on synaptic formation in culture : Exogenously added BDNF stimulated the synaptic formation of rat cerebral cortex neurons in culture.
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