基于AMPA受体自噬研究电针影响AD突触可塑性的作用机制

The ability of learning and memory decline clinical manifestations of Alzheimer's disease.It is associated with synaptic plasticity.The highly variable membrane(extrapolation, internalization, recycling or degradation) of ionotropic glutamate AMPA receptors in the postsynaptic membrane postsynaptic is the key factor affecting on synaptic plasticity.Autophagy is one form of cell death, also a kind of self protection mechanism in the homeostasis of intracellular environment.It plays an important role in response to stimulation,in clear abnormal protein,and in internal and external environment.Recent study has shown that the degradation of autophagy on AMPAR is the necessary steps to maintain synaptic plasticity (long-term depression formation),and autophagy participate in the pathological changes of AD.Our previous study confirmed that electroacupuncture can regulate the expression of AMPAR and its insert related protein GRIP and NSF,and the synaptic plasticity.At present, the study of relationship between the number of AMPAR and the activity of autophagy in AD,and which between the number of AMPAR and electroacupuncture on AD rats,has not been reported.The project,from early pathological changes of LTD easy and the degradation activity of autophagy of AMPAR in AD,will investigate the effects of Electroacupuncture on it.And the project is in order to initially revealed the mechanism and provide theoretical basis of electroacupuncture in the treatment of AD.

学习记忆能力下降是阿尔茨海默病的主要临床表现，与突触可塑性变化相关。突触后膜离子型谷氨酸AMPA受体在突触后膜上的高度可变性（外插、内化、再循环或降解）是影响突触可塑性的关键环节。自噬即细胞死亡的一种方式，更是一种自我保护机制，在维持细胞内环境的稳态，清理异常蛋白及对内外环境的刺激应答方面有重要作用。近期有研究表明，自噬对AMPAR的降解是维持突触可塑性（长时程抑制形成）的必要步骤，并可参与AD病理变化的多个环节。前期我们研究证实，电针可调节AMPAR及其插入锚定相关蛋白GRIP、NSF等蛋白表达，调节突触可塑性。目前探讨AD中AMPAR的数量及自噬的活性的变化关系，及电针对AD大鼠AMPAR数量与自噬之间调节作用的研究未见报道。本项目创新性的从AD早期病理变化中LTD易化及自噬对AMPAR降解活性角度，探讨电针干预对其影响，以期初步揭示电针治疗AD的作用机制，并为临床治疗提供理论依据。