Effects Of Maternal Separation On Depressive-Like Behaviors In Adult C57BL/6 Female Mice And Its Mechanism

Objectives Separation induced early-life stress may cause abnormal brain development,nerve endocrine disorders and oxidative stress and then have a profound impact on adult behavior.In this paper,we used the C57BL/6 female mice as the object.Through the maternal separation during lactation and chronic unpredictable stress in adult,we studied the influence of maternal separation on adult depressive-like behavior and the correlation between brain total protein oxidative modification and depression,so as to explore the effect of early-life stress on the mechanism of depression-like behavior development.Methods C57BL/6 female mice were divided into four groups: Control group,the female mice without any treatment from birth;MS group,the female mice exposed to maternal separation from birth and normally fed to adulthood after treatment;MS+CUS group,the female mice exposed to maternal separation from birth and exposed to chronic unpredictable stress during adulthood;CUS group,the female mice without any treatment at birth and exposed to chronic unpredictable stress during adulthood.Sucrose preference test was used to detect depression-like behavior in adult.The level of protein carbonylation and cysteine nitrosylation in prefrontal cortex and amygdala were detected through western blot.Real-time fluorescent quantitative PCR was used to detect the mRNA expression levels of SOD,CAT,BDNF and GR in the prefrontal cortex,amygdala and hippocampus.Results(1)Before chronic unpredictable stress,the sucrose preference percentage of MS group was not significantly different from that of Control group;after chronic unpredictable stress,the sucrose preference percentage of MS+CUS group was significantly lower than that of Control group and CUS group,while there was no significant difference between the preference level of CUS group and Control group.(2)Before chronic unpredictable stress,the protein carbonylation in prefrontal cortex ofMS group increased significantly,the protein carbonylation and cysteine nitrosylation in amygdala did not change significantly;after chronic unpredictable stress,the protein carbonylation and cysteine nitrosylation in prefrontal cortex of MS+CUS group increased significantly,the protein carbonylation in prefrontal cortex of CUS group increased significantly,while the protein carbonylation and cysteine nitrosylation in amygdala did not change significantly.(3)Before chronic unpredictable stress,we found that the expression levels of SOD mRNA in prefrontal cortex and the expression levels of BDNF,GR,SOD m RNA in hippocampus of MS group decreased significantly;after chronic unpredictable stress,we found that the expression levels of BDNF,SOD mRNA in hippocampus and the expression levels of SOD mRNA in prefrontal cortex of MS+CUS group decreased significantly.Conclusions Early-life stress caused by maternal separation can lead to decreased anti-depression ability in female mice,and it is more likely to induce depressive-like behavior under stress conditions.The decreased expression levels of antioxidant enzymes gene and the increased amount of protein carbonylation and nitrosylation in brain are potential reasons for higher likelihood of development of depression-like behavior among mice with maternal separation experience.