中链脂肪酸联合α-亚麻酸对APP/PS1转基因小鼠学习记忆行为及大脑Aβ42、Tau蛋白表达的影响

Effects of medium-chain fatty acid and α-linolenic acid on learning, memory behavior and expressions of Aβ42, Tau protein in brain in APP/PS1 transgenic mice

目的探讨中链脂肪酸(medium-chain fatty acid,MCFA)和α-亚麻酸(α-linolenic acid,ALA)对APP/PS1转基因小鼠学习记忆功能及大脑Aβ42、Tau蛋白表达的影响。方法将25只4周龄APP/PS1转基因小鼠随机分为ALA+MCFA组(8只)、MCFA组(9只)和长链脂肪酸(long chain fatty acid,LCFA)组(8只,对照组),同窝野生型小鼠为WT组(10只,正常对照组)。各组小鼠用不同脂肪酸配制饲料连续喂养至36周龄,用Morris水迷宫进行定位航行实验和空间探索实验,并记录平均逃避潜伏期、平台穿越次数和平台象限滞留时间百分比。免疫组化法检测海马Aβ沉积,Western blot方法检测APP、Aβ42蛋白及Tau蛋白表达。结果与LCFA组小鼠相比,ALA+MCFA组和MCFA组小鼠水迷宫定位航行试验平均逃避潜伏期明显缩短(P<0.05),空间探索试验平台穿越次数则明显较高(P<0.05),海马组织Aβ斑块数目相对较少,且皮质和海马Aβ42蛋白及Tau蛋白表达均较低(P<0.05)。结论与LCFA相比,ALA和MCFA能通过减少Aβ42蛋白生成及Tau蛋白磷酸化水平,改善APP/PS1转基因小鼠学习记忆功能,具有潜在的延缓阿尔茨海默病发生和进展的作用。

Objective To investigate the effects of medium-chain fatty acid （MCFA） and α-linolenic acid （ALA） on learning and memory behavior of APP/PS1 transgenic mice and expression levels of Aβ42, Tau protein in their brains. Methods Twentyfive APP/PS 1 transgenic mice, aged 4 weeks, were randomly divided into ALA＋MCFA group （combined intervention group, n=8）, MCFA group （intervention group, n=9） and long chain fatty acid （LCFA） group （control group, n=8） according to their fasting body weight, and another 10 wild type mice （WT） served as normal control group. The mice were fed diets with different fatty acid formulas for 36 weeks. Then Morris water maze was used to perform place navigation test and spatial probe test, meanwhile the average escape latency, time across the platform and time percent during platform quadrant were recorded. Immunohistochemical assay was used to detect A β deposition in hippocampus, and the APP, Aβ42 and Tan protein levels were detected by western blot. Results Compared with LCFA group, the average escape latency of Morris water maze place navigation test in ALA＋MCFA and MCFA group reduced significantly （P 〈 0.05）, and the time across the platform on probe day was significantly greater （P 〈 0.05）, Aβ plaques in hippocampus were relatively less, and the level of Aβ42 and Tau protein in cortex and hippocampus were relatively lower （P 〈 0.05）. Conclusion ALA and MCFA can improve the learning and memory function of the APP/PS1 transgenic mice by reducing the production of Aβ42 protein and the phosphorylation of Tau protein, therefore they may have the potential to delay the development and progress of Alzheimer＇s disease.