| Co-Investigator(Kenkyū-buntansha) |
TABUCHI Akiko Toyama Med.& Pharm.Univ., Fac.Pharm.Sci., Assistant Prof., 薬学部, 講師 (40303234)
IMAMURA Lisa Toyama Med.& Pharm.Univ., Fac.Pharm.Sci., Head Researcher, 薬学部, 助手 (10232620)
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| Budget Amount *help |
¥10,700,000 (Direct Cost: ¥10,700,000)
Fiscal Year 2004: ¥4,400,000 (Direct Cost: ¥4,400,000)
Fiscal Year 2003: ¥6,300,000 (Direct Cost: ¥6,300,000)
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| Research Abstract |
Brain -derived nauotrophic factor (BDNF), a member of the neuzotrophin family, plays an important role in promoting neuronal survival, differentiation and synaptic plasticity. The BDNF gene consists of four short 5'-exons (exons I, II, III and IV) and a common 3'-exon V encoding a prepro-BDNF and four promoters, BDNF promoter I, II, III and IV (BDNF-PI, -PII, -PIII and -PIV) are located upstream of the 5'-exons, respectively. In this study, we demonstrated that the expression of BDNF exon III transcripts was secondarily induced by an administration of BDNF to the rat cortical neuronal cells in culture. This secondary induction was caused 24 hrs after the primary induction. And required the activation of TrkB receptors and the Ca^<2+> signalings for it. The regulational systems for this secondary induction is thought to be involeved in a consolidation of memory in the brain. On the other hand, the maximum expression of PACAP (pituitary adenylate cyclase-activating polypeptide) mRNA and its maximum promoter activity was obtained by a simultaneous addition of Ca^<2+> and cAMP signals in neurons. These signals can be evoked via activation of NMDA and dopamine D1 receptors, respetively., which is involeved in reward learning and drug addiction. In addition, we found that the PACAP mRNA stability was prolonged by the Ca^<2+> signals, which may be involved in synaptic plasticity. Finally, we found that neuro-restrictive silencing factor (NRSF) was repressive to the BDNF-PI and that the activation of BDNF-PI was induced irrespective of the repression of BDNF-PI by NRSF. This mechanisms regulating the BDNF exon I mRNA expression seems to be involved in the differentiation of neuronal stem cells in the dentate gyrus of hippocampus. We have already established the multi-screening method for surveying the drugs that are effective to enhance the BDNF gene transcription.
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