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

本项目旨在分析神经营养因子，特别是脑源性神经营养因子（BDNF）在突触传递中的作用及其分子基础。BDNF的作用根据其时间窗口分为急性或慢性两个阶段，根据其作用部位（突触前或突触后）分为两类。项目在各个类别的结果如下：急性反应-突触前：BDNF诱导培养的小脑颗粒神经元释放兴奋性氨基酸神经递质、谷氨酸和天冬氨酸（Brain Res. 1999，神经科学）。> 2000)。导致释放的信号级联反应揭示了BDNF- trkb激活-PLC激活-细胞内储存ca2 +释放- na +流入-谷氨酸/谷氨酸释放的反向运输（JNR.2000）突触后：BDNF增加NMDA电流并诱导NMBD受体亚基磷酸化。它们都是由Fynkinase介导的，Fynkinase被BDNF激活（在SFN会议2000上提出）。慢性作用：突触前：BDNF分别增加基底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蛋白和囊泡单胺转运蛋白2的表达（论文正在准备中）。突触后：BDNF增加AMPA受体亚基蛋白水平，增强AMPA电流，同时诱导一些与AMPA受体相互作用的PDZ蛋白（论文准备中）。

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).