胎盘糖皮质激素受体低表达对孕期抑郁模型雌性子代的影响

Knockdown of NR3C1 in perinatal depressed mice produced depressive-like behaviors in female offspring

目的探索糖皮质激素受体(GR)对孕期抑郁小鼠子代抑郁倾向的影响。方法利用普通小鼠进行孕期抑郁(PND)造模,并用Western blot检测不同性别胎盘绒毛中GR表达情况;利用转基因工具鼠获得胎盘GR敲低小鼠,共20只。Western blot检测胎盘GR敲低效果并分析胎盘组织学改变;对胎盘GR敲低小鼠进行孕期抑郁造模,比较GR敲低组抑郁孕鼠的仔鼠(KD)与GR非敲低组仔鼠(N-KD)生长发育情况;动物行为实验检测仔鼠运动能力和抑郁倾向。结果PND小鼠雌性仔鼠胎盘绒毛GR表达显著升高(P<0.05);胎盘GR敲低小鼠的胎盘GR表达显著降低(P<0.05);KD组仔鼠胎盘形态未见异常(P>0.05);KD组仔鼠生长发育未见异常(P>0.05);KD组仔鼠成年后运动能力未见异常(P>0.05);KD组雌性仔鼠在成年后更有抑郁倾向(P<0.05)。结论敲低胎盘GR可能增加孕期抑郁小鼠雌性子代抑郁倾向。

Objective To explore the role of glucocorticoid receptors(GRs)in the depressive-like behaviors of offspring of perinatally depressed mice(PND).Methods Western blot was applied to detect the expression of GRs in PND mice generated with wild-type mice.Twenty mice with the placenta GR knocked down were generated using transgenic mice.Then western blot was used to verify the knockdown of the GRs in the mice,and the morphology of the mice was analyzed.Pregnant GRs knocked down mice were stimulated continuously to be used to compare the growth and development of offspring of the GRs knockdown group(KD)and the GRs non-knockdown group(N-KD);The locomotion behaviors and depressive-like behaviors of each group′s offspring were detected by open field test(OFT)and the forced swimming test(FST).Results Compared with the control group,the level of GRs was increased in the placenta of female offspring of PND mice(P<0.05);The expression of GRs in placenta of KD decreased significantly(P<0.05);We observed no significant differences between the KD and N-KD in placental morphology(P>0.05);The growth and development and the exercise capacity of the KD and N-KD showed no significant differences(P>0.05);However,the female offspring of KD had more depressive tendencies than the male offspring(P<0.05).Conclusion A decrease in placental GRs augments the tendency of female offspring of PND mice to depression.