早期母爱剥夺影响边缘系统-丘脑-皮质环路致大鼠成年后抑郁的机制研究

Study on influences of early life maternal deprivation on limbic-thalamic-cortical circuitry which are associated with depression in adult rats

目的观察早期母爱剥夺应激对边缘系统-丘脑-皮质环路重要组成部分前额叶、海马、丘脑的神经元及GFAP表达的影响,探索早期应激造成成年后抑郁样表现的病理机制。方法新生大鼠按照随机数字表分为母爱剥夺组(n=20)和对照组(n=20)。母爱剥夺组幼鼠出生后1~14 d予母爱剥夺应激,对照组不予任何处理。待大鼠2个月龄时进行抑郁样行为学评估,后处死取脑,分别行Neun和GFAP免疫荧光染色,共聚焦显微镜下观察拍照,ImageJ计数阳性细胞数,进行统计学分析。结果母爱剥夺组大鼠与对照组大鼠相比,出现快感缺失、社交主动性降低等抑郁样行为表现;其前额叶、海马区及丘脑Neun阳性细胞数少于对照组,差异有统计学意义(P<0.05);GFAP免疫荧光染色结果显示母爱剥夺组大鼠前额叶、海马区及丘脑GFAP阳性细胞计数少于对照组,差异有统计学意义(P<0.05)。结论出生后早期母爱剥夺可致大鼠成年后出现抑郁样行为表现,而早期母爱剥夺可致边缘系统-丘脑-皮质环路的重要组成部分前额叶、海马及丘脑区的神经元及星形胶质细胞数目显著减少,推测边缘系统-丘脑-皮质环路可能参与早年应激致成年后抑郁的病理机制。

Objective To investigate the effects of maternal deprivationon neuron and expression of GFAP in prefrontal,hippocampus and thalamus,which are important components of limbic-thalamic cortical circuitry,and to explore the pathological mechanisms of maternal deprivationcausing adult depression-like manifestations.Methods Newborn rats were divided into two groups:maternal deprivation group(n=20)and control group(n=20)by random number table method.Rats in maternal deprivationgroup were exposed to maternal deprivation(3 hours per day)from postnatal day 1 to 14 while rats in control group were not.The sucrose preference and sociability tests were conducted when the rats were two months old.Then all the rats were sacrificed and their brains were collected,and the immunofluorescence staining were applied on Neun and GFAP.The confocal microscope was used for observation and photography,and the ImageJ was used for the number of positive cells and statistical analysis.Results Compared with the control group,the maternal deprivation group showed depression-like behaviors such as anhedonia and reduced social initiative,and the number of Neun positive cells in the prefrontal lobe,hippocampus and thalamus in the maternal deprivation group was less than that in the control group,with statistical significance(P<0.05).The results of GFAP immunofluorescence staining showed that the number of GFAP positive cells in the prefrontal lobe,hippocampus and thalamus in the maternal deprivation group was lower than that in the control group,and the difference was statistically significant(P<0.05).Conclusion Maternal deprivation can cause to depressed behaviors in adult rats and downregulates the numbers of neuron and astrocyte in prefrontal,hippocampus and thalamus-important parts of limbic-thalamic-cortical circuitry that might be involved in the mechanisms of maternal deprivationcaused adult depression.