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SCREENING FOR ANTIDEPRESSANT RELATED GENES RELATED TO NEUROGENESIS

筛选与神经发生相关的抗抑郁药相关基因

基本信息

批准号：
18591323
负责人：
YAMADA Mitsuhiko
金额：
$ 2.49万
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：
2006
资助国家：
日本
起止时间：
2006 至 2007
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-18591323/
关键词：
ANTIDEPRESSANT ECT NEUROGENESIS DIFFERENTIAL CLONING 電気けいれん経頭蓋的磁気刺激小胞体

项目摘要

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.

我们以前进行EST分析，以确定一些负责抗抑郁作用的分子机制。迄今为止，已从大鼠脑组织中分离到几个抗抑郁相关基因（ADRGs）的部分cDNA片段。然后我们利用这些ADRG基因开发了我们最初的cDNA微阵列（ADRG微阵列）。最近，在实验模型中，抗抑郁药的慢性治疗增加了成年海马神经发生。ECT是另一种疗法，特别用于治疗耐药抑郁症，也上调成人。最近的一项研究还表明，海马体的辐射，减少海马体神经发生，消除抗抑郁药的行为影响。这些观察结果表明，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芯片来鉴定与神经发生相关的ADRG，作为抑郁症的治疗机制之一。在这些基因中，我们重点关注ADRG116和ADRG604，这两个基因都是大鼠神经丝氨酸蛋白酶抑制剂的代表。免疫组化显示，大鼠神经丝氨酸蛋白酶抑制剂在SGZ的内部表达。部分免疫反应阳性细胞出现在门部和门部与SGZ之间的区域。而颗粒细胞层的其它区域则无免疫标记细胞表达。实时荧光定量PCR检测大鼠神经丝氨酸蛋白酶抑制剂在分化的神经干细胞中的表达。分化后96小时，与分化前细胞相比，neuroserpin mRNA表达显着增加。总之，我们的结果可能支持神经丝氨酸蛋白酶介导的神经系统的可塑性变化的假设，并参与抗抑郁药和ECT的治疗作用。