氟西汀对8月龄APP/PS1小鼠海马齿状回内胆碱能神经元作用的体视学研究

Effects of fluoxetine on cholinergic neurons in dentate gyrus of 8-month-old APP/PS1 mice: a stereological study

目的探讨给予氟西汀(fluoxetine, FLX)干预后,8月龄APP/PS1小鼠海马齿状回(dentate gyrus,DG)内胆碱能神经元的总数以及密度的变化,分析认知功能的改善是否与FLX干预后DG区内胆碱能神经元数量变化有关。方法选用20只8月龄雌性APP/PS1小鼠,采用完全随机法分为对照组和干预组,分别给予8周生理盐水和等量FLX腹腔注射后,进行Morris水迷宫测试以检测小鼠学习和记忆能力;运用体视学方法计算两组小鼠海马DG区内胆碱能神经元的总数和密度;运用酶联免疫吸附剂测定胆碱能相关神经递质。结果水迷宫实验结果显示,干预组的逃避潜伏期较对照组明显缩短(P<0.05)。体视学结果显示,FLX显著增加了APP/PS1小鼠海马DG区内胆碱能神经元的数量和密度(P<0.01);酶联免疫吸附实验结果显示,FLX增加了8月龄APP/PS1小鼠海马乙酰胆碱(acetylcholine, ACh)含量(P<0.01)。结论海马DG区内胆碱能神经元总数的变化以及海马ACh含量的变化可能与FLX干预后8月龄APP/PS1小鼠行为学的改变有关。

Objective To investigate the change of the total number and density of cholinergic neurons in dentate gyrus(DG)of hippocampus of 8-month-old APP/PS1 mice after fluoxetine(FLX)intervention and analyze whether the improvement of cognitive function is related to the change of the number of cholinergic neurons after FLX intervention.Methods Twenty 8-month-old female APP/PS1 mice were randomly divided into control group and intervention group.The mice in the control group and the intervention group were given 8 weeks of normal saline and the same amount of FLX by intraperitoneal injection,Then,Morris water maze test was used to test the learning and memory ability of the mice.The total number and density of the cholinergic neurons in the DG were calculated using stereological methods.The cholinergic-related neurotransmitters were determined by enzyme-linked immunosorbent assay.Results The results of Morris water maze test showed that the escape latency of the intervention group was significantly shorter than that of the control group(P<0.05).The results of stereological findings showed that FLX significantly increased the total number and density of cholinergic neurons in the DG of hippocampus of 8-month-old APP/PS1 mice(P<0.01);The results of enzyme linked immunosorbent assay showed that FLX statistically increased the level of acetylcholine(ACh)in the hippocampus of APP/PS1 mice(P<0.01).Conclusion The change of the total number of cholinergic neurons in the DG of hippocampus and the level of ACh in the hippocampus may be related to the behavioral changes of 8-month-old APP/PS1 mice after FLX intervention.