CRMP-2介导的早年应激对成年后应激抵抗的影响及其神经可塑性机制研究

个体应对应激时会出现应激敏感和应激抵抗两种不同状态。早年应激会影响成年后个体对应激的反应。脑衰反应调节蛋白（CRMP-2）影响细胞支架微管系统微管二聚体的聚合或解聚，从而调节轴突和树突的生长，参与神经可塑性过程。其他学者及我们的前期研究显示CRMP-2和应激及海马神经元可塑性有关，提示CRMP-2可能通过调节微管系统参与抑郁症神经可塑性过程。但应激抵抗模型CRMP-2介导的细胞支架微管相关的神经可塑性机制尚未明了。本项目拟建立早年母爱剥夺应激模型，成年后给予CUMS，探讨CRMP-2介导的早年应激对成年后应激反应的影响。进一步地，幼年沉默CRMP-2，检测改变的CRMP-2对成年后应激抵抗的影响及细胞支架微管系统、神经可塑性改变；并从细胞水平进一步验证。由此从CRMP-2及所属的细胞支架微管系统角度，探索抑郁症应激抵抗神经可塑性损伤的新视角，为药物的新靶点提供有益的研究基础。

Individual subjected to stress may express two different phenotypes: Stress-sensitive and stress-resistance. Early stresses in the form of childhood stresses may affect individual reactivity to stress and coping in adult stage. Numerous functions for Collapsing Response Mediator Protein-2 (CRMP-2) have been identified related to various functions in neuroplasticity. Function important to our investigation is the ability of CRMP-2 to regulate axon and dendrite outgrowth via transport and stabilization of microtubule dimers, as well as enhancement of tubulin’s intrinsic GTPase activity for microtubule depolymerization. . Several studies, including our previously study, have shown that CRMP-2 is involved in stress and neuronal plasticity of hippocampus. These studies suggest that CRMP-2 may involve in neuronal plasticity in depression via microtubular regulation. However, the role of CRPM-2 in neuronal plasticity of stress resistance phenotype and stress sensitive and the mechanism of CRMP-2 involving in microtubular system associated neuroplasticity remain unclear and need more researches. . The primary aim of the present study is to investigate possible alteration of CRMP-2 protein involved in the effects of early stress on adult stress resilience and the neuroplasticity mechanisms. Early stress model is established by exposing the rat to stress in early stage. After the rats reach adult stage, they will be exposed to chronic unpredictable mild stress (CUMS) in order to explore the effect of early stress on the reaction to the adult CUMS. Furthermore, by silencing CRMP-2 and increasing or decreasing CRMP-2 phosphorylation in rat pup, we may discuss how the change in CRMP-2 expression and activation may affect stress resistance, microtubular system and neuroplasticity in adult stage on cellular level after the rats are exposed to adult CUMS. We hope to open up a new angle to look into neuronal plasticity of stress resistance in depression via CRMP-2 and subordinate cytoskeletal microtubular system. Our study may provide helpful exploration for new antidepressant drug target.