SCREENING FOR ANTIDEPRESSANT RELATED GENES RELATED TO NEUROGENESIS

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We have previously performed EST analysis to identify some molecular machinery responsible for antidepressant effect. To date, several partial cDNA fragments as antidepressant related genes/ESTs (ADRGs) were isolated from rat brain. Then we developed our original cDNA microarray (ADRG microarray) using these ADRG genes Recently, in experimental models, chronic treatment of antidepressant increased adult hippocampal neurogenesis in robust. ECT that is another therapy particularly used in the treatment of drug-resistant depression, also up-regulated adult. A recent study also demonstrates that irradiation of the hippocampus, which reduces hippocampal neurogenesis, abolishes the behavioral effects of the antidepressant. These observations suggest that hippocampal neurogenesis may play an important role in the therapeutic mechanisms of depression. In the present study, we used ADRG microarray to identify the ADRGs that related to neurogenesis as one of the therapeutic mechanisms of depression. Among the genes, we focused on ADRG116 and ADRG604, both of which were represented rat neuroserpin. Immunohistochemical analysis showed that rat neuroserpin was expressed in the inner of SGZ. Some of the immunoreactive cells were present in hilus and in the area between hilus and SGZ. On the other hand, no immunolabeling cells were expressed in other area of granule cell layer. The expression of rat neuroserpin in the differentiated neuronal stem cells was analyzed by real-time quantitative PCR. 96hr after differentiation, the neuroserpin mRNA expression was significantly increased when compared to the cells before differentiation. In conclusion, our results may support the hypothesis that neuroserpin mediated plastic changes of nervous system and are involved with therapeutic action of antidepressants and ECT.