APP17肽对APP转基因小鼠突触相关蛋白表达的影响

目的研究APP17肽对APP转基因小鼠(APP V717 I)海马神经元突触相关蛋白表达的影响。方法将3 mon龄的APP转基因小鼠随机分为模型组和APP17肽治疗组(皮下注射0.16 mg.kg-1.d-1,每周3次),并以相同年龄和背景的C57BL/6 J小鼠做正常对照组。7 mon后行Morris水迷宫测定,小鼠脑组织灌注固定后进行PSD-95、Shank1蛋白的免疫组化染色。结果模型组小鼠水迷宫实验的逃避潜伏期明显长于治疗组和正常对照组,且模型组小鼠大脑海马CA4区中的PSD-95、Shank1阳性反应神经元明显减少,染色浅;APP17肽治疗组与正常对照组相近。结论APP转基因小鼠大脑中存在突触后致密区蛋白表达异常,由此引起突触功能损害,进而导致记忆、学习能力的改变;而APP17肽能通过提高PSD-95、Shank1的表达,使突触的损伤接近恢复正常。并能改善小鼠的记忆、学习能力。

Effect of APP17 peptide on the expression of synaptic associated protein in amyloid precursor protein transgenic mice

Aim To investigate the effect of amyloid protein precursor(APP)-17 peptide on the expression of synaptic associated protein in neurons of hippocampus of APP V717I transgenic mice.Methods The transgenic mice were randomly divided into model group and APP17 peptide treatment group.In latter group,the mice were injected APP17 peptide 0.16 mg·kg~(-1) each day and three time a week.The same age and background C57BL/6J mice were used in normal control.Seven month later,water maze testing of behavior was conducted;fixative was injected into the mice and cryostat section were analyzed with immunohistochemistry for PSD-95 and Shank1.Results ① Full-course swimming time was obviously longer in model group than these in treatment,and control group,and the results were similar to Group C with APP17 petide treatment.② In model group,the expression of PSD-95 and Shank1 decreased.Treatment group normalize expression of the targeted proteins.Conclusion There were low PSD-95 and Shank1 levels in the brain of APP transgenic mice.APP17 peptide improves the expression of PSD-95 and Shank1;therefore it may improve learning ability and memory.