孕晚期炎症暴露对中老年子鼠海马谷氨酸受体1含量及与认知损害相关性研究

Effect of prenatal inflammation on hippocampal glutamate receptor 1 level in the middle-aged mice and the correlation with cognitive function impairment

目的探讨孕晚期炎症暴露对中老年子鼠海马谷氨酸受体1(GluR1)含量改变及其与空间学习记忆能力改变的相关性。方法母鼠孕第15~17天每天经腹腔注射脂多糖(LPS,50μg/kg),生理盐水组注射等容积生理盐水。子鼠分别视为LPS组和生理盐水组,均于3月龄和15月龄时完成Morris水迷宫任务。蛋白质印迹实验检测海马GluR1含量。结果 15月龄生理盐水组比3月龄生理盐水组和15月龄LPS组比同龄生理盐水组在Morris水迷宫中学习期游泳路程延长,记忆期靶象限的游泳路程百分比下降,差异有统计学意义(均P<0.05),海马GluR1水平下降,差异有统计学意义(均P<0.01)。相关分析表明仅15月龄小鼠的海马GluR1水平与小鼠游泳路程呈负相关,与靶象限的游泳路程百分比呈正相关。结论中老年CD-1小鼠海马GluR1含量下降,且与空间学习记忆损害相关,及其母亲孕晚期炎症暴露会加速这种下降。

Objective To investigate the changes of age-related hippocampal glutamate receptor 1 level and its correlation with spatial learning and memory ability in CD-1 mice exposed to inflammation during late pregnancy.Methods Maternal mice were intraperitoneally injected with lipopolysaccharide(LPS, 50μg/kg) or normal saline at days 15~17 of pregnancy. Their offspring were treated as LPS group and normal saline group, and completed Morris water maze at the age of 3 months and 15 months respectively. The level of GluR1 was detected by Western blotting.Results The 15-month normal saline group(compared to the 3-month normal saline group) and the 15-month LPS group(compared to 15-month normal saline group) had longer swimming distanceand lower swimming distance percentage in the target quadrant(all P<0.05) in the Morris water maze, with statistical significance and lower hippocampal GluR1 levels( all P < 0. 01). The difference had statistical significance. Correlation analysis showed that only the hippocamppal level of GluR1 in the 15-month mice negatively correlated with swimming distance and positively correlated with the percentage of swimming distance in target quadrant. Conclusion The results suggest that the middle-aged CD-1 mice decrease GluR1 content of hippocampus which correlates with impaired ability of spatial learning and memory,and maternal exposure to inflammation in the late pregnancy accelerate this change.