氟西汀早期干预对改善APP/PS1小鼠认知障碍和海马突触可塑性的作用

Effect of Early Intervention of Fluoxetine Improves Cognitive Impairment and Hippocampal Synaptic Plasticity in APP/PS1 Mice

目的研究氟西汀早期干预对阿尔茨海默病(Alzheimer’s disease,AD)转基因小鼠认知功能障碍和突触可塑性的影响及潜在机制。方法雄性阿尔茨海默病APP/PS1双转基因(APPswePSEN1dE9)小鼠24只,随机分为AD模型组(AD组)和氟西汀干预组(FLX组),并以12只野生型小鼠作为对照组(Con组)。从2月龄起,FLX组小鼠开始连续15 d的氟西汀水溶液(浓度1 g·L^(-1))腹腔注射给药,AD组和Con组小鼠接受等体积的生理盐水腹腔注射,给药结束4个月后(相当于6月龄时)水迷宫实验检测小鼠认知功能,电生理检测小鼠海马突触可塑性,免疫印迹检测海马中突触相关蛋白表达水平,酶联免疫吸附试验(ELISA)检测海马中淀粉样蛋白-β(Aβ)含量。结果氟西汀早期干预可有效改善AD转基因小鼠的认知功能障碍和海马神经元细胞突触可塑性,增加AD转基因小鼠海马中突触相关蛋白的表达水平,并降低海马Aβ含量。结论氟西汀早期干预能有效改善AD转基因小鼠认知功能和突触可塑性造成的损伤。

Objective To study the effect and potential mechanism of early intervention of fluoxetine on cognitive dysfunction and synaptic plasticity in Alzheimer’s disease(AD)transgenic mice.Methods 24 male Alzheimer’s disease APP/PS1 double transgenic(APPswePSEN1dE9)mice were randomly divided into AD model group and fluoxetine intervention group(FLX),and 12 wild-type mice were selected as controls.From 2 months of age,mice in the FLX group received fluoxetine in aqueous solution(concentration 1 g·L^(-1))by intraperitoneal injection for 15 d;and mice in the AD and control groups received saline by intraperitoneal injection in an equal volume.Four months after the end of drug administration(equivalent to 6 months of age),the water maze test was used to detect cognitive function,electrophysiological test was used to detect synaptic plasticity in the mouse hippocampus,immunoblotting was used to detect the expression level of synapse-associated proteins in the hippocampus,and ELISA was used to detect the content of amyloid-β(Aβ)in the hippocampus.Results Early intervention with fluoxetine effectively improved cognitive dysfunction and synaptic plasticity of hippocampal neuronal cells,increased the expression level of synapse-associated proteins in the hippocampus,and decreased hippocampal Aβcontent in AD transgenic mice.Conclusion Early intervention with fluoxetine effectively ameliorates the impairment of cognitive function and synaptic plasticity caused by AD lesions in AD transgenic mice.