权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

THE EXPRESSION OF SYNAPTIC VESICLE PROTEINS AFTER CHRONIC ANTIDEPRESSANT TREATMENT IN RAT BRAIN.

长期抗抑郁药治疗后大鼠脑内突触小泡蛋白的表达。

基本信息

批准号：
16591162
负责人：
YAMADA Mitsuhiko
金额：
$ 2.3万
依托单位：
NATIONAL CENTER OF NEUROLOGY AND PSYCHIATRY
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2004
资助国家：
日本
起止时间：
2004 至 2005
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-16591162/
关键词：
ANTIDEPRESSANT PRESYNAPSE NEUROTRANSMITTER EXOCYTOSIS SYNAPTIC VESICLE うつ病タンパク

项目摘要

The biological basis for the therapeutic mechanisms of depression are still unknown. We have previously performed EST analysis and identified some common biological changes induced after chronic antidepressant treatment as antidepressant related genes/ESTs : ADRG#1-707. Then, we developed our original cDNA microarray on which ADRG#1-707 were spotted, for rapid secondary screening of candidate genes as the novel therapeutic targets. With this microarray, we found that the expression of some of the ADRGs were related to neurotransmiter release and located on synaptic vesicle. Indeeed, VAMP2/synaptobrevin, cysteine string protein, synapsin I, Rab-1A and Rab-3B were induced after chronic sertraline treatment in rat frontal cortex. Western blot analysis also demonstrated the induction of these ADRGs at protein levels after chronic treatment with imipramine and sertraline. In addition, synaptophysin and secretogranin II, often used as a marker protein for small synaptic vesicle or large dense core granule were significantly increased after chronically treatment with antidepressants. On the other hand, the expression of SNAP-25 and syntaxin-1, which are used as markers for synapse and make a SNARE-complex with VAMP2, were not affected by these treatments. These results suggested that the number of synaptic vesicles, but not the number of synapses, was increased after chronic antidepressant treatment. The synaptic vesicles and proteins may be a new target molecular system for antidepressant.

抑郁症治疗机制的生物学基础仍然未知。我们以前进行了EST分析，并确定了一些常见的生物学变化后，慢性抗抑郁药治疗的抗抑郁药相关基因/EST：ADRG#1-707。然后，我们开发了我们的原始cDNA微阵列，其上点样ADRG#1-707，用于快速二次筛选候选基因作为新的治疗靶点。利用该芯片，我们发现一些ADRGs的表达与神经递质的释放有关，并定位于突触小泡上。事实上，大鼠额叶皮质经慢性舍曲林处理后，VAMP 2/synaptobrevin、半胱氨酸串蛋白、synapsin I、Rab-1A和Rab-3B被诱导。蛋白质印迹分析也表明，这些ADRGs的诱导与丙咪嗪和舍曲林慢性治疗后，在蛋白质水平。此外，突触素和分泌粒蛋白II，通常被用作小突触囊泡或大致密核心颗粒的标记蛋白，在抗抑郁药长期治疗后显著增加。另一方面，SNAP-25和syntaxin-1的表达不受这些处理的影响，SNAP-25和syntaxin-1被用作突触的标记物并与VAMP 2形成SNARE复合物。这些结果表明，突触囊泡的数量，而不是突触的数量，慢性抗抑郁药治疗后增加。突触囊泡和突触蛋白可能成为抗抑郁药的新靶分子系统。