外源性NGF对APP/PS1转基因小鼠学习记忆能力的影响

Effects of exogenous NGF on learning and memory abilities of the APP/PS1 transgenic mice

目的观察外源性神经生长因子(nerve growth factor,NGF)对APP/PS1转基因小鼠学习记忆能力的影响和环磷酸腺苷反应元件结合蛋白(cAMP response element bling protein,CREB)蛋白的调节作用。方法实验分为野生组(雄性5月龄C57BL/6小鼠6只,鼻腔给予生理盐水),AD组(雄性5月龄APP/PS1小鼠6只)和AD+NGF组(雄性5月龄APP/PS1小鼠6只,鼻腔给予小鼠NGF治疗14w),应用Morris水迷宫检测小鼠的学习记忆能力变化,应用Western blot检测小鼠脑内CREB蛋白、p-CREB蛋白的表达。结果 AD+NGF组小鼠的潜伏期和找到平台前所经过的总路程均显著低于AD组小鼠,经过目标平台位置的次数明显高于AD组小鼠,游泳总路程和平均游泳速度均明显低于AD组小鼠。外源性NGF上调APP/PS1转基因小鼠脑内CREB蛋白和p-CREB蛋白的表达。结论外源性NGF改善APP/PS1转基因小鼠的学习记忆能力可能与上调CREB和p-CREB蛋白的表达相关。

Objective To study the effects of exogenous NGF on learning and memory abilities and the expression of CREB protein in the APP/PS1 transgenic mice. Methods The mice were divided into： wild group, APP/PS1transgenic group and APP/PS1＋ NGF group（treated with NGF via nasal cavity for 14 weeks）. Morris water maze test was applied to examine the changes of learning and memory of the mice. Western blot technique was used to test the expressions of CREB proteins and p-CREB proteins in the mice brain. Results The escape latency and the total distance of finding platforms, the total swimming distances and the average swimming speeds were notably lower in AD＋NGF group than in AD mice, but the times of passing target platform location were obviously higher in AD＋NGF group than in AD mice. The exogenous NGF upregulated the expressions of CREB proteins and p-CREB proteins in brain of APP/PS1 transgenic mice. Conclusion The improvement of learning and memory abilities of the APP/PS1 transgenic mice by exogenous NGF might be related to upregulation of CREB and p-CREB protein expression.