抑郁症大鼠内侧前额叶皮层PNNs表达及GABA能神经元功能改变

Expression of PNNs and the functional changes of GABA-ergic neurons in the medial prefrontal cortex in a rat model of depression

目的:探究慢性不可预见性温和应激(CUMS)诱导的抑郁模型大鼠内侧前额叶皮层(mPFC)中神经元周围基质网络(PNNs)与γ-氨基丁酸(GABA)能神经元功能的变化。方法:将28只大鼠随机分为两组,模型组采取CUMS建立抑郁模型,对照组不做任何处理。采用免疫荧光双标技术检测PNNs密度以及PNNs与小清蛋白(PV)双标阳性神经元(PNNs+PV+)占PV阳性(PV+)神经元百分比;Western印迹法检测大鼠PNNs主要组分蛋白聚集蛋白聚糖(Aggrecan)、短小蛋白聚糖(Brevican)、GABA主要合成酶谷氨酸脱羧酶67(GAD67)的蛋白表达。结果:模型组mPFC脑区PNNs密度及PNNs+PV+神经元占PV+神经元百分比较对照组均降低,差异具有统计学意义(P<0.05);模型组mPFC脑区中Aggrecan、Brevican及GAD67蛋白表达水平较对照组减少,差异有统计学意义(P<0.01)。结论:慢性不可预见性温和应激造模的抑郁症模型大鼠mPFC脑区PNNs表达及GABA主要合成酶GAD67蛋白表达水平下降。

Objective:To investigate the effects of chronic unpredictable mild stress(CUMS)on perineuronal nets(PNNs)andγ-aminobutyric acid(GABA)-ergic neurons in the medial prefrontal cortex(mPFC)of adult rats.Methods:Totally 28 rats were randomly divided into two groups.The model group adopted CUMS to establish a depression model,and the control group did not receive any treatment.The density of PNNs and the percentage of PNNs positive(PNNs+)and parvalbumin positive(PV+)neurons in total PV+neurons in the mPFC were detected by immunofluorescence.The protein expression of main components of PNNs,Aggrecan and Brevican,and GABA main synthase glutamic acid decarboxylase 67(GAD67)in the mPFC were detected by Western blot.Results:The density of PNNs and the percentage of PNNs+and PV+neurons in total PV+neurons in the mPFC in the model group were decreased compared with the control group(P<0.05);The expression levels of PNNs component proteins Aggrecan and Brevican,and GABA main synthase GAD67 were also decreased in the model group(P<0.01).Conclusion:The levels of PNNs and GABA synthase GAD67 in the mPFC of rats were decreased after chronic unpredictable mild stress.