N-硬脂酰丝氨酸对APP/PS1转基因小鼠学习记忆及运动能力的影响

Effect of N-stearoylserine on learning, memory and exercise capacity of APP/PS1 mice

目的 研究N-硬脂酰丝氨酸(NSS)能否通过大麻素Ⅱ型(CB2)受体改善APP/PS1转基因小鼠行为学异常现象。方法 采用9月龄APP/PS1转基因小鼠模拟阿尔茨海默病模型;通过开场实验观察小鼠自主活动能力,疲劳转棒仪实验观察小鼠运动协调及抗疲劳能力,水迷宫实验观察小鼠学习记忆功能,通过ELISA方法测定β-淀粉样蛋白(Aβ)42及Aβ40水平,通过Western blot方法测定CB2蛋白表达水平。结果 NSS(2 mg/kg和5 mg/kg)能提高转基因小鼠运动协调及学习记忆能力,降低脑组织Aβ42及Aβ40水平,上调CB2蛋白水平;CB2受体拮抗剂AM630能抑制上述现象。结论 NSS改善APP/PS1转基因小鼠学习记忆障碍及运动失调,降低转基因小鼠海马组织Aβ42及Aβ40水平,此机制可能是通过CB2受体实现。

Objective To study whether N-stearoyl serine(NSS)could improve behavioral abnormalities in APP/PS1 transgenic mice through CB2 receptor.Methods The APP/PS1 transgenic mouse was used to study the animal behavior through open field test,rotarod experiment and Morris water maze,The levels ofβ-amyloid(Aβ)42 and Aβ40 were determined by ELISA,and the expression level of CB2 protein was determined by Western blot.Results NSS(2 mg/kg and 5 mg/kg)could increase the coordinative movement and the ability of learning and memory,decrease the level of Aβ42 and Aβ40 and increase the expressions of CB2.The CB2 receptor antagonist AM630 could reverse the above phenomenon.Conclusion NSS could improve spatial learning and memory impairments and motor dysfunction in APP/PS1 transgenic mice and decrease the levels of Aβ42 and Aβ40 in the hippocampus,and the mechanism may be achieved by regulating the CB2 receptor signaling pathway.