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

抑郁症治疗机制的生物学基础尚不清楚。我们之前进行了EST分析，并确定了慢性抗抑郁药物治疗后引起的一些常见生物学变化为抗抑郁相关基因/ESTs: adrg# 1-707。然后，我们开发了我们的原始cDNA微阵列，adrg# 1-707被发现，用于快速二次筛选候选基因作为新的治疗靶点。通过该芯片，我们发现一些ADRGs的表达与神经递质释放有关，并且位于突触囊泡上。慢性舍曲林可诱导大鼠额叶皮层VAMP2/synaptobrevin、半胱氨酸串蛋白、synapsin I、Rab-1A和Rab-3B。Western blot分析还显示，长期使用丙咪嗪和曲林治疗后，这些ADRGs在蛋白水平上被诱导。此外，长期服用抗抑郁药后，常被用作小突触囊泡或大致密核颗粒标记蛋白的synaptophysin和secretogranin II显著升高。另一方面，作为突触标记并与VAMP2形成snare复合物的SNAP-25和syntaxin-1的表达不受这些处理的影响。这些结果表明，慢性抗抑郁药物治疗后突触囊泡数量增加，而突触数量没有增加。突触小泡和蛋白可能是抗抑郁药物的新靶点分子系统。

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.