有氧运动对调节AD模型小鼠海马Ras/Drebrin增加树突棘可塑性分析

Aerobic Exercise Improves Dendritic Spine Plasticity by Regulating Ras/Drebrin in Hippocampus of APP/PS1 Transgenic Mice

目的:探讨有氧运动对AD模型APP/PS1转基因小鼠海马树突棘可塑性的作用。方法:5月龄清洁级雄性APP/PS1小鼠40只,随机分为APP/PS1安静组(AS组)、APP/PS1运动组(AE组);同月龄的雄性C57BL/6J小鼠20只作为对照组(CS组)。运动组小鼠进行12周跑台运动。运动方案为前10 min运动速度15 m/min,后50 min速度18 m/min,跑台坡度为0°,5 d/周,60 min/d,共12周。跳台回避实验和旋转杆平衡实验检测小鼠行为学变化;免疫组织化学法检测Aβ多聚体含量;Golgi染色法检测海马CA1和CA3区树突棘密度;Western blot检测海马CA1和CA3区Ras、Drebrin的蛋白表达。结果:12周有氧运动可明显提高APP/PS1小鼠的行为学表现,降低多聚体Aβ斑块的含量,增加Drebrin、Ras蛋白表达,增加海马CA1和CA3区树突棘密度。结论:规律有氧运动可以有效抑制8月龄APP/PS1小鼠海马多聚体Aβ沉积,通过增加Ras、Drebrin含量,缓解AD时树突棘的丢失,增加树突棘可塑性,是运动改善其行为学能力的分子机制之一。

Objective:To investigate the effect of aerobic exercise on Ras and development regulation brain protein(Drebrin)in the hippocampus of 8-month-old APP/PS1 transgenic mice,providing a theoretical basis for promoting the density and plasticity of dendritic spine by aerobic exercise.Methods:APP/PS1 transgenic mice(5 months old)were randomly divided into 12 weeks exercise group(AE)and sedentary group(AS)respectively,and C57 BL/6 J mice(5 months old)as the control group(CS).After exercise,the behavioral change was detected by step-down fear conditioning and rotarod test.The levels of Aβwere tested by immunohistochemistry.The density and morphology of dentritic spine were detected by FD Golgi Staining Kit.The protein levels of Ras and Drebrin were measured by Western Blotting.Results:Aβwas aggregated at the hippocampus in 8-month-old APP/PS1 transgenic mice and the plaque burden was declined in AE.Twelve weeks aerobic exercise significantly improved performances on step-down fear conditioning and rotarod test in APP/PS1 mice,increased the density of dendritic spine and the expression of Ras and Drebrin in the hippocampus.Conclusions:Regular aerobic exercise can effectively reduce the level of Aβand increase the expressions of Ras and Drebrin,resulting in improving the density and plasticity of dendrite spine in the hippocampus of 8-month-old APP/PS1 transgenic mice.Thus,regular aerobic exercise would rescue dendritic spine loss under neuropathological conditions.