蛇床子素对APP/PS1小鼠学习记忆功能及脑内Aβ产生的影响

Effect of osthole on learning and memory function of APP/PS1 mice and Aβ production in brain

目的观察蛇床子素(OST)对APP/PS1小鼠学习记忆功能及Aβ产生的影响。方法雄性APP/PS1小鼠分为模型对照和OST给药组,野生型(WT)小鼠作为正常对照。自小鼠9月龄始每天灌胃1次OST 10 mg/kg,对照组小鼠给予等体积的双蒸水,连续给药12周。每月观察小鼠筑巢行为;Morris水迷宫观察小鼠空间学习记忆功能;Nissl染色观察海马神经元的形态及数量;Western blot检测海马组织Aβ1-40和Aβ1-42含量,APP、α分泌酶(ADAM10)及β分泌酶(BACE1)的蛋白表达水平。结果APP/PS1小鼠筑巢行为较WT小鼠略有变差,但评分在各组间的差异没有统计学意义。与WT小鼠相比,APP/PS1小鼠出现明显的空间学习记忆能力的下降,表现为平均逃避潜伏期明显延长且目标象限停留时间百分比和穿越平台次数明显减少;海马Aβ1-40和Aβ1-42含量增加;神经元形态受损、数量减少;APP及BACE1蛋白呈高表达,而ADAM10的蛋白表达下降。给予OST后,改善了APP/PS1小鼠空间学习记忆功能;减少了海马组织Aβ含量;降低了APP及BACE1蛋白表达,增加了ADAM10的蛋白表达。结论OST改善APP/PS1小鼠的认知功能,可能与减少海马组织Aβ的含量有关。

Objective To observe the effects of osthole(OST)on the learning and memory function of APP/PS1 mice and Aβproduction in brain.Methods Male APP/PS1 transgenic mice were randomly divided into control and OST groups,wild type(WT)mice were served as normal control.Nine-month-old mice were subjected to OST(10 mg/kg body weight)by gavage once day for 12 weeks in OST group,while mice were received equal volume double distilled water as control.Nesting behavior assay was monthly observed during administration,and Morris water maze was performed followed by brain collection.The contents of Aβ1-40 and Aβ1-42 as well as the protein expression of APP,ADAM10 and BACE1 in hippocampus were detected by Western blotting.Results Compared with WT mice,the nesting behavior of APP/PS1 mice was lightly worsen,but no significant difference was found;the learning and memory ability of APP/PS1 mice was significantly decreased,including the prolonged average escape latency and shortened the percentage of target quadrant residence time,and the reduced number of times crossing the platform.The contents of Aβ1-40 and Aβ1-42 were increased in hippocampus of APP/PS1 mice compared with WT mice.Additionally,the neurons in DG and CA3 regions were morphologically damaged,and the number of neurons was significantly decreased,the expressions of APP and BACE1 proteins were increased,while ADAM10 protein expression was decreased.After OST treatment,the learning and memory function of APP/PS1 mice was improved.In addition,the contents of Aβand the expressions of APP and BACE1 in hippocampus were down-regulated,while ADAM10 protein expression was up-regulated.Conclusion The effect of OST improving the cognitive ability of APP/PS1 mice may be related to reducing the contents of Aβin hippocampus.