早期母婴分离对大鼠海马GFAP表达的影响

The effect of early maternal deprivation on the GFAP expression of rats in hippocampus

目的比较早年母婴分离对大鼠海马GFAP(Glial fibrillary acidic protein,胶质细胞原纤维酸性蛋白)表达的影响及成年后行为学的改变,探讨与抑郁相关的可能机制。方法出生后3天(PND3)的新生雄性鼠从第4天开始和母鼠分开,分为应激敏感组(每天分离时间3h)、应激抵抗组(每天分离时间15min)、正常对照组,每组各20只,持续一周。PND12开始处死一半的取大鼠海马,分别进行蛋白免疫印迹和免疫组化实验检测GFAP,比较不同组GFAP的表达量。PND56开始对剩下的大鼠进行旷场实验和强迫游泳,评价行为学差异。结果母婴分离时间长的大鼠(应激敏感组)与正常组大鼠相比,蛋白免疫印迹和免疫组化结果一致,海马GFAP表达量减少,差异有统计学意义(P<0.05)。母婴分离时间短的大鼠(应激抵抗组)和正常组大鼠相比,海马GFAP表达量差异无统计学意义(P>0.05)。母婴分离时间长的大鼠,成年后表现出旷场总移动距离减少,中心移动距离减少,强迫游泳中不动时间延长,差异有统计学意义(P<0.05)。结论长时间母婴分离使幼年大鼠海马GFAP表达减少,成年后出现抑郁样行为,可能和星形胶质细胞重吸收谷氨酸减少影响突触可塑性有关。

Objective To compare the influence of early maternal deprivation on the expression of GFAP（Glial fibrillary acidic protein）in rats＇ hippocampus and behavior changes in adults,particularly to discuss the underlying mechanisms between astrocytes and depression. Methods On day 4 of parturition,neonatal pups were separated from their mothers during PND4（the day of post natal 4）to PND11 by transparent polyethylene sheet. Litters were randomly assigned to three groups ：stress sensitive group（a daily 3-hour maternal separation）stress resilient group（a daily 15-min maternal separation）normal control group. Each group contained 20 samples and half of the rats were sacrificed for hippocampus on PND12. The expression of GFAP were tested by western blot and IHC. The remaining rats were tested in the open field and their immobility time in forced swimming test on PND56. Results Compared with normal group,SSM groups（PND56）showed decreased total distance and central distance（P〈0.05）due to maternal deprivation while SRM not. The immobility time significantly increased for SSM group in forced swimming test（P〈0.05）. Compared with normal group,the GFAP levels were significantly decreased in SSM group（P〈0.05）. Conclusion Early long time maternal deprivation downregulates the expression of GFAP in hippocampus and leads to depressed behavior in adult rats. The underlying mechanism may be associated with astrocytes less uptake of glutamate which affects synaptic plasticity.