孕前应激诱导的产后抑郁模型小鼠海马精神分裂症断裂基因1的表达变化

Expression of Disrupted-in-schizophrenia 1 in Hippocampus in Postpartum Depression Animal Models Induced by Pre-pregnancy Stress

目的以孕前应激诱导方式建立产后抑郁症(PPD)小鼠模型,评估母鼠产后的异常行为,检测母鼠海马精神分裂症断裂基因1(DISC1)及血清雌二醇、皮质酮的变化,揭示产后抑郁的发病机制。方法将32只Balb/c母鼠采用随机数字表法分为对照组和模型组,每组16只,对照组小鼠不给予任何刺激,模型组小鼠给予慢性束缚刺激。3周后对照组和模型组均予雌雄合笼交配怀孕,分娩后即为对照组和孕前应激诱导PPD模型组。于分娩后3周对母鼠进行旷场测试、悬尾测试及糖水偏爱测试以评价造模是否成功。取海马检测DISC1基因及蛋白的表达,眼眶取血检测血清雌二醇及皮质酮水平。结果产后3周,与对照组相比,PPD模型组在旷场测试中自发活动无改变(P>0.05),在悬尾测试中的绝望不动时间显著增加(t=-4.950,P<0.001),糖水偏爱显著降低(t=2.475,P<0.05)。与对照组相比,PPD模型组海马DISC1基因(t=-8.915,P<0.001)及蛋白(t=-5.004,P<0.01)表达均显著上调,而血清皮质酮及雌二醇均无变化(P均>0.05)。结论慢性孕前应激可诱导Balb/c母鼠表现出产后抑郁样症状,其发病机制可能与调控海马DISC1的基因和蛋白表达有关。

Objective To establish a postpartum depression animal model induced by pre-pregnancy stress,assess abnormal maternal depressive-like behavior,observe the expression of disrupted-in-schizophrenia 1（ DISC1） in the hippocampus,and detect serum estradiol and corticosterone. Methods A total of 32 female Balb/c were assigned to two groups using random number table： the control group and the pre-pregnancy stressed group（ model group）,and the model group was subjected to 3 weeks of chronic restraint stress. After the last stressor,the control group and the model group were housed with a male. About 4 weeks later,the mice gave birth to pups. Then at 3 weeks postpartum,open field test,tail suspension test,and sucrose preference test were carried out. The expressions of DISC1 mRNA and protein of hippocampus were detected by real-time quantitative polymerase chain reaction and Western blot,respectively. The serum levels of estradiol and corticosterone were detected with enzyme linked immunosorbent assay. Results After 3 weeks of postpartum,the model mice showed depression-like behaviors. In the open field test,there was no effect on the total distance moved or time spent in the center field（ P〉0. 05）. Immobility in tail suspension test was significantly increased（ t =-4. 950,P〈0. 001） and sucrose preference was significantly reduced in model group（ t = 2. 475,P〈0. 05）.There was significant statistical difference between control and model group on the expression of DISC1 mRNA（ t =-8. 915,P〈0. 001） and protein（ t =-5. 004,P〈0. 01） in hippocampus. There was no significant statistical difference on estradiol and corticosterone between two groups（ P〉0. 05）. Conclusions Chronic prepregnancy stress can induce dams into postpartum depression. The pathogenesis of postpartum depression may be related to the regulation of DISC1 in the hippocampus.