The expression of synaptic vesicle proteins after chronic antidepressant treatment in rat brain

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. Indeed, VAMP2/synaptobrevin, cysteine string protein, synapsin 1, 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 11, 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.