反转录转座子LINE-1在非躯体伤害诱导的大鼠PTSD样行为中的作用与机制

神经元内基因组稳定性的维持是保证个体内稳态与适应环境的基础。反转录转座子长散在原件-1(LINE-1)的表达与活性增加促进了基因组的不稳定性。我们前期研究发现在非躯体伤害诱导的创伤后应激障碍（PTSD）样大鼠海马和杏仁核中LINE-1 的表达出现显著上调，同时伴随有系列基因表达与DNA甲基化调节相关蛋白的改变。我们认为：LINE-1表达的上调与激活可能是个体不能正常适应应激反应的核心，大鼠遭受应激后，通过表观遗传学机制使海马与杏仁核内LINE-1表达上调，引起神经元内基因组的不稳定性增加，动物回到与应激相似场景，海马与杏仁核内系列基因的表达急剧改变，恐惧记忆唤起，PTSD样症候群出现。本项目将综合运用形态学、行为学、分子生物学等方法对我们的假说进行验证，从"基因组不稳定性"的角度探讨PTSD的发病机制，为PTSD的治疗提供新的靶点。

Genomic stability in the neurons is the basis of keeping individuals' homeostasis and adapting themselves to the environment. The expression and activation of long interspersed nucleotide element-1 (LINE-1) promote genomic instability. Our previous study found that the expression of LINE-1 in the hippocampus and amygdale was significantly up-regulated in the non physical injury PTSD rats. Meanwhile, the expression of a series of genes and DNA methylated regulation proteins were also altered in the hippocampus and amygdale of non physical injury PTSD rats. We suppose that after a sever stress, LINE-1 is significantly up-regulated in the hippocampus and amygdale through an epigenetic modification, then the genomic stability of neurons is disturbed, thus when retrieved to the context similar to the traumatic event, a series of genes are remarkably altered in the hippocampus and amygdale, which leads to the re-experiencing of the traumatic event, and the PTSD syndrome appears. It is reasonable for us to assume that the activation of LINE-1 might induce an inability to adapt to the normal stress. The project intend to verify the hypothesis using morphologic, behavioral and biological methods, to explore the mechanisms of PTSD from the point of genomic instability which might provide a new target of PTSD treatment.