妊娠期慢性应激对不同性别子代抑郁的影响

目的 探讨妊娠期慢性应激对不同性别子代小鼠抑郁程度的影响及其可能机制.方法 实验分为妊娠期正常处理-子代正常处理(Control)组、妊娠期慢性应激-子代正常处理(CPS)组、妊娠期正常处理-子代慢性应激(COS)组、妊娠期慢性应激-子代慢性应激(COS+CPS)组.通过强迫游泳实验观察子代小鼠的抑郁程度;HE染色观察子代小鼠海马CA 3区神经元病理组织形态变化;Western blot法检测小鼠海马中雷帕霉素靶蛋白(mTOR)的表达量;ELISA法检测小鼠血清中促肾上腺皮质激素释放激素(CRH)的含量.结果 与Control组相比,子代雄鼠COS组不动时间延长(P<0.05),海马CA 3区神经元细胞损伤的数目明显增加,神经元排列疏松、紊乱,核固缩、浓染;海马组织中mTOR表达量减少(P<0.05);血清CRH浓度升高(P<0.05);子代雌鼠COS组不动时间延长(P<0.05),海马组织中mTOR表达量减少(P<0.05),其余指标未呈现类似结果.与COS组相比,子代雄鼠COS+CPS组不动时间延长(P<0.05),海马CA 3区神经元进一步损伤,海马组织中mTOR的表达量减少(P<0.05),血清中CRH浓度升高(P<0.05);子代雌鼠COS+CPS组的上述指标亦未进一步改变.结论 妊娠期慢性应激进一步加剧慢性应激所致的子代雄鼠抑郁,其机制可能与其升高小鼠血清CRH水平,抑制mTOR的表达,最终引起海马CA 3区神经元损伤有关.妊娠期慢性应激未能进一步加剧子代雌鼠应激所致的抑郁程度.

Effect of chronic prenatal stress on depression in different sex of offspring mice

Objective To explore the effect of chronic prenatal stress on depression in different sex of offspring mice, and the possible mechanism.Methods Offspring mice were randomly devided into four groups: the prenatal control-offspring control group(control group), the chronic prenatal stress-offspring control group(CPS group), the prenatal control-chronic offspring stress group(COS group), and the chronic prenatal stress-chronic offspring stress group(COS+CPS group).Forced swimming test was used to investigate depression in mice, and the histopathologic changes in CA 3 field of the hippocampus were examined under a light microscope.Additionally,Western blot was used to observe the expression of mammalian target of rapamycin(mTOR) expression in hippocampus.Furthermore, ELISA was used to examine the serum levels of corticotropin-releasing hormone(CRH) in the offspring mice.Results Compared with the control group, the results showed that male offspring mice in COS group had more motionless time (P<0.05), and the neuropathological changes were characterized by the disintegrated pyramidal layered structure, decreased neuron number, worse cell morphology, soma condensation, nuclear pyknosis in the CA 3 field of hippocampus in the COS group(P<0.05).Moreover, the expression of mTOR in hippocampus were decreased, and the serum CRH concentration in the COS group were increased(P<0.05).There were no similar results in COS group of female offspring except that the motionless time was extended(P<0.05) and the expression of mTOR in hippocampus were decreased(P<0.05).Noteworthy, the motionless time and neuropathological changes stated above were worsen in COS+CPS group of male offspring mice than those in COS group(P<0.05).There were also no similar results in COS+CPS group of female offspring.Conclusion Chronic stress may exacerbate the level of depression in male offspring mice who also suffer chronic stress, which may be related to chronic prenatal stress reduce the production of mTOR through increasing expression of CRH resulted the neuropathological changes in the CA 3 field of hippocampus.Chronic prenatal stress could not exacerbate the degree of depression elicited by chronic stress in female offspring mice.