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Effects of neurotrophins on the regulation of synaptic molecules and on the synaptic functions

神经营养素对突触分子调节和突触功能的影响

基本信息

批准号：
11680752
负责人：
TAKEI Nobuyuki
金额：
$ 2.3万
依托单位：
NIIGATA UNIVERSITY
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
1999
资助国家：
日本
起止时间：
1999 至 2000
项目状态：
已结题

项目摘要

The aim of this project is the analysis of the action of neurotrophins, especially BDNF (brain-derived neurotrophic factors), on synaptic transmission and the elucidation of its molecular basis. The effects of BDNF is classified into 2 phases (acute or chronic)by its time window and also 2 categories depending on its site of action (pre- or post-synaptic). The results of the project in each categories are as follows.ACUTE ACTIONPre-Synapric : BDNF induced release of excitatory amino acid neurotroansmitters, glutamate and aspartate from cerebellar granule neurons in culture (Brain Res. 1999, Neurosci. Res. 2000). The signaling cascades which leaded to the release was revealed that BDNF-TrkB activation -PLC activation-Ca2+release from intracellular store-Na+ influx-reverse transport of glutamate/glutamate release (JNR.2000)Post-Synaptic : BDNF increased NMDA current and induced phosphorylation of NMBD receptor subunit. Both of them are mediated by Fynkinase, which activated by BDNF (presented at SFN meeting 2000).CHRONIC ACTIONPre-Synaptic : BDNF increased the expression of vesicular acetylcholine transporter and vesicular monoamine transporter2 in basalforebrain cholinergic and midbrain dopaminergic neurons, respectively (papers in preparation).Post-Synaptic : BDNF increased the levels of AMPA receptor subunit proteins and enhanced AMPA current, together with the induction of the some PDZ proteins which interacted with AMPA receptor (paper in preparation).

本项目的目的是分析神经营养因子，特别是脑源性神经营养因子在突触传递中的作用，并阐明其分子基础。根据脑源性神经营养因子的作用部位(突触前或突触后)，脑源性神经营养因子的作用可分为急性或慢性两个阶段。实验结果如下：急性神经营养因子诱导培养的小脑颗粒神经元释放兴奋性氨基酸递质、谷氨酸和天冬氨酸(Brain Res.1999，Neurosci)。决议2000)。BDNF-TrkB激活-PLC激活-细胞内钙离子释放-Na+内流-谷氨酸/谷氨酸释放的反向转运(JNR.2000)突触后：BDNF增加NMDA电流并诱导NMBD受体亚单位的磷酸化。它们都是由Fynkinase介导的(在2000年SFN会议上发表)。慢性作用-突触：BDNF分别增加基础前脑胆碱能神经元和中脑多巴胺能神经元中囊泡乙酰胆碱转运体和囊泡单胺转运体2的表达(论文正在准备中)。突触后：BDNF增加AMPA受体亚单位蛋白的水平，增强AMPA电流，并诱导一些与AMPA受体相互作用的PDZ蛋白(论文正在准备中)。