青春期慢性应激调节小鼠成年期心理韧性的性别差异研究OA

Objective To explore the influence of chronic stress during adolescence on resilience in adulthood and its sex differences using a mouse model.Methods We constructed a mouse model combining adolescent chronic restraint stress(CRS)with adult learned helplessness(LH)evaluation.During adolescence(4～7 weeks of age),the experimental group was subjected to CRS for 2 hi/d for 21 d,while the control(Ctrl)group was raised under standard conditions.At 7 weeks of age,locomotor activity,anxiety-like behavior,spatial memory,and depression-like behavior were assessed using the open field test,elevated plus maze,Y-maze,and forced swimming test(FST),respectively.Mice in both groups were housed normally from 8～11 weeks of age,and the FST was repeated in the 10th week to observe the long-term effects of adolescent CRS on adult behavior.When they reached adulthood(11～14 weeks of age),all mice underwent LH training,and the escape latency and number of failures were measured to evaluate their sensitivity to acute stress and psychological resilience.Results Adolescent CRS resulted in a significant reduction in body mass in both male and female mice(all P＜0.000 1).Behavioral tests revealed a significant increase in immobility time in the FST in the experimental group(all P＜0.01),with no significant differences in the other behavioral tests(all P＞0.05).After a 3-weeks recovery period,body mass in the experimental group remained lower than in the control group(male P＜0.05,female P＜0.001);however,the difference in immobility time in the FST was no longer significant(all P＞0.05).Mice were found as adults by LH test,among male mice,the proportion of susceptible individuals in the experimental group was significantly higher compared with the control group(P＜0.05),but there was no significant difference in the proportion of resilient individuals.In contrast,there was no significant difference in either the susceptible or resilient proportion between the experimental and control groups among female mice.Conclusions The impact of adolescent chronic stress on psychological resilience in mice exhibits sex-specific differences:male,but not female mice,demonstrate a long-term reduction in psychological resilience.This model can provide a reference for in-depth investigations into the mechanisms underlying sex differences in adolescent stress and adult depression,and for developing corresponding interventional strategies.