围绝经期小鼠抑郁样行为及相关脑区GABA_A受体的改变

Changes of depressive-like behavior and GABA_A receptors in related brain regions in perimenopausal mice

目的研究围绝经期小鼠抑郁样行为及相关脑区GABAA受体的改变。方法采用2、8、12m雌性C57BL/6小鼠,采用悬尾实验、强迫游泳实验检测小鼠不动时间的变化,研究小鼠抑郁样行为的改变。进一步,采用实时定量PCR方法检测海马,前额叶皮质中GABAA受体Gabra1、Gabrb2及Gabrg2的mRNA改变。结果三组小鼠在悬尾实验、强迫游泳实验中不动时间无明显差异(P>0.05);海马、前额叶皮质中Gabra1、Gabrb2在12m组小鼠明显降低(P<0.05);海马中Gabra1水平在3组之间呈逐渐下降,而前额叶皮质中Gabra1,海马、前额叶皮质中Gabrb2在8m组呈一定程度上升,至12m时明显下降(P<0.05);海马及前额叶皮质中Gabrg2在3组之间无明显差异(P>0.05)。结论无应激状态下,围绝经期小鼠抑郁样行为无明显变化;小鼠海马及前额叶皮质中Gabrg2可能参与该行为过程;海马、前额叶皮质中Gabra1,Gabrb2在围绝经期明显下降,可能参与应激诱导的围绝经期抑郁易感性。

Objective To study changes of depressive-like behaviors and GABA A receptors in related brain regions in perimenopausal mice.Methods Female C57BL/6 mice of 2 m,8 m and 12 m were used in the current study.The immobility time in tail suspension test(TST)and forced swim test(FST)were detected to evaluate the changes of depressive-like behavior in mice.Furthermore,real-time quantitative PCR was used to detect mRNA changes of GABA A receptors Gabra1,Gabrb2 and Gabrg2 in the hippocampus and prefrontal cortex.Results There was no significant difference in the immobility time among the three groups of mice in the TST and FST(P>0.05).The Gabra1 as well as Gabrb2 in the hippocampus and prefrontal cortex were significantly decreased in the 12 m group(P<0.05);the mRNA level of Gabra1 decreased gradually with aging of the three groups,while Gabra1 in the prefrontal cortex,Gabrb2 in the hippocampus and prefrontal cortex increased to a certain extent in the 8 m group,and then decreased significantly at 12 m(P<0.05).There was no significant difference in Gabrg2 among the three groups in the hippocampus and prefrontal cortex(P>0.05).Conclusion There was no significant change in depressive-like behavior in perimenopausal mice without stress;Gabrg2 in the hippocampus and prefrontal cortex might be involved in this behavioral process in mice;Gabra1 and Gabrb2 in the hippocampus and prefrontal cortex were significantly decreased during perimenopause,which might be involved in stress-induced perimenopausal depression susceptibility.