JNK信号参与成年动物海马SGZ区神经发生机制的研究

项目名称： JNK信号参与成年动物海马SGZ区神经发生机制的研究

项目编号： No.31070936

项目类型： 面上项目

立项/批准年度： 2011

项目学科： 金属学与金属工艺

项目作者： 陈聚涛

作者单位： 中国科学技术大学

项目金额： 8万元

中文摘要： 本项目拟采用Jnk基因敲除鼠，通过电生理、生化和免疫组织染色的方法研究了JNK在海马突触可塑性，SGZ区神经发生过程中的作用。由于动物繁殖缓慢，我们在免疫组化实验中主要验证了与新神经元增殖、分化相关抗体的有效性。电生理实验研究了MAPK在去增强效应，LTD中的作用以及在体LTD诱导与睡眠之间的关系。研究发现JNK在去增强效应中的前期过程起重要调节作用，在后期作用不明显；p38则参与了去增强效应的后期，前期不参与；而ERK在该条件诱发的去增强效应中作用不明显；免疫印迹结果表明，JNK、ERK和p38的磷酸化水平与电生理结果相吻合。另外研究发现JNK，ERK和p38不同程度的参与了LTD的诱导和维持。同时我们发现在体LTD易于在白天或者睡眠剥夺的情况下被诱导，而在夜晚则很难诱导出来，说明LTD与高的睡眠压力有关。这也说明在体诱导LTD过程中，睡眠压力是影响LTD诱导的一个很重要的因素。

中文关键词： JNK；海马；MAPK；神经发生；突触可塑性

英文摘要： By using electrophysiological,biochemical and immunohistochemistrical method, we studied the role of JNK in synaptic plasticity and adult neurogenesis in hippocampal subgranular zone in jnk deficient mice. Our study show that the JNK signal pathway is invovled in the early phase of depotentiation but not the late phase. The western blotting analysis indicate that the JNK phosphorylation is significantly reduced at the early phase in the presence of JNK inhibitor, but there is no significant difference after depotentiaiton induction for 1 or 2 hours compared with the control.While the p38 MAPK activation is required in late phase of depotentiation but not early phase, western blotting show significant reduction of p38 phosphorylation after LFS application 2 hour. The ERK signal pathway does not invovle in regulation of depotentiation. The western blot analysis reveal the unchanged ERK phosphoyrlaion level after depotentiation induction. Also the JNK, ERK and p38 was partly invovled in regulation LTD.Next we studied the effects of day,night and sleep pressure in the induction of LTD in hippocampus in vivo, we found that LTD can be easily induced in day but not at night.If we deprived sleep in daytime, the LTD can be induced at night, which indicate that LTD induction is correlate with sleep presure. Our results show that sleep presurre should be taken into account as one of the key factors in LTD induction in vivo. Due to the less available Jnk deficient mice, we first test the validity of antibody for the proliferation and differentiation in adult neurogenesis in control mice.

英文关键词： JNK;himpocampus;MAPK;neurogenesis; synaptic plasticity