SCREENING FOR ANTIDEPRESSANT RELATED GENES RELATED TO NEUROGENESIS

我们之前已经进行了EST分析，以确定一些与抗抑郁作用有关的分子机制。到目前为止，已从大鼠脑中分离到几个抗抑郁相关基因/EST(ADRGs)的部分cDNA片段。然后我们利用这些ADRG基因构建了我们独创的基因芯片(ADRG微阵列)，在实验模型上，慢性抗抑郁药物治疗增加了成年海马神经发生的健壮性。ECT是另一种特别用于治疗耐药性抑郁症的疗法，也上调了成年人的表达。最近的一项研究还表明，照射海马区会减少海马区的神经发生，从而消除抗抑郁剂的行为影响。这些观察表明，海马神经发生可能在抑郁症的治疗机制中发挥重要作用。在本研究中，我们使用ADRG微阵列来鉴定与神经发生相关的ADRGs，作为抑郁症的治疗机制之一。在这些基因中，我们重点研究了ADRG116和ADRG604，这两个基因都代表了大鼠神经丝氨酸。免疫组织化学分析显示，大鼠神经丝氨酸蛋白在SGZ内有表达。部分免疫反应阳性细胞位于门区和门区与SGZ之间的区域。颗粒细胞层的其他区域未见免疫标记细胞表达。用实时荧光定量聚合酶链式反应分析大鼠神经干细胞中神经丝蛋白的表达。分化后96h，与分化前相比，神经丝蛋白基因的表达显著增加。综上所述，我们的结果可能支持神经丝氨酸介导神经系统可塑性改变的假说，并参与了抗抑郁药物和ECT的治疗作用。

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.