慢性子代应激改善妊娠期慢性应激诱导的子代雄鼠抑郁

The chronic offspring stress ameliorated the depression-like behavior and pathological damage in male offspring mice caused by chronic stress during pregnancy

目的探讨妊娠期慢性应激(CSDP)联合慢性子代应激(COS)在诱导子代雄性小鼠抑郁的作用和机制。方法将C57/BL6J孕鼠分为正常处理组和慢性应激组,子鼠出生后选取雄性子鼠,分为妊娠期正常对照+子代正常对照组(NC+NC组)、妊娠期正常对照+子代慢性应激组(NC+COS组)、妊娠期慢性应激+子代正常对照组(CSDP+NC组)、妊娠期慢性应激+子代慢性应激组(CSDP+COS组)。通过强迫游泳实验和高架十字迷宫实验检测子鼠的抑郁程度;运用高尔基染色法观察海马CA3区神经元树突损伤;使用TUNEL染色观察海马CA3区神经元凋亡情况;采用Western blot技术测定海马组织mTOR和p-mTOR(Ser2448)蛋白含量,计算mTOR蛋白活性。结果妊娠期慢性应激引起子代雄鼠抑郁样行为,导致海马CA3区神经元树突损伤和神经元凋亡,mTOR蛋白活性降低。当子鼠再经历慢性应激后,可改善妊娠期慢性应激诱导的雄性子代小鼠抑郁样行为,降低海马CA3区神经元凋亡指数,减轻CA3区神经元树突损伤,同时提高了mTOR蛋白活性。结论妊娠期慢性应激可致雄性子代小鼠出现抑郁样行为,慢性子代应激可以改善由妊娠期慢性应激所诱导的雄性子代小鼠的抑郁样行为和海马CA3区的神经元树突损伤和凋亡,慢性子代应激可能通过调节mTOR信号通路来改善由妊娠期慢性应激引起的子代抑郁样行为。

Objective To investigate the interactional roles and mechanism of the chronic stress during pregnancy(CSDP)and chronic offspring stress(COS)exposures in inducing male offspring depression.Methods The pregnant mice were randomly divided into the normal control group and the chronic stress group.After the offspring were born,male offspring were randomly divided into the normal control+normal control group(NC+NC),the normal control+chronic offspring stress group(NC+COS),the chronic stress during pregnancy+normal control group(CSDP+NC)and the chronic stress during pregnancy+chronic offspring stress group(CSDP+COS).The depression related indices in male offspring mice were detected by forced swim test and elevated plus maze.Pathological changes in hippocampus CA3 area were assessed by Golgi staining and TUNEL staining.The activity of hippocampal mTOR was investigated by using the Western blot to quantitatively detect the expression of mTOR and p-mTOR(Ser2448).Results Chronic stress during pregnancy induced depressive symptoms in male offspring accompanied by neuronal damage and apoptosis in the hippocampus and reduced mTOR activity.The chronic offspring stress ameliorated the depression-like behavior and pathological damage of hippocampal CA3 region in male offspring mice that caused by chronic stress during pregnancy.And the chronic offspring stress elevated mTOR activity.Conclusion Chronic stress during pregnancy induced depressive symptoms in male offspring.The chronic stress could ameliorate the depression-like behavior,neuronal damage and neuronal apoptosis in hippocampal CA3 region of male offspring mice that caused by chronic stress during pregnancy.The chronic offspring stress may improve the depression-like behavior of offspring caused by chronic stress during pregnancy through regulating mTOR activity by corticotropin releasing hormone(CRH).