Effects Of Early Life Stress On Depression- And Anxiety-like Behaviours And BDNF Expression In Male Mice And Effects Of Intervention In Different Periods

Objective: Early life is a critical period of neuron growth and development as well as synapse formation.Early life stress(ELS)will have different degrees of adverse effects on individual's physical and psychological development,and participates in the formation of certain diseases or behavioral susceptibility factors,thus inducing the increase of individuals' depression-and anxiety-like behaviors in adulthood.Therefore,we through the establishment of early life stress model,compare in adolescence and adulthood by Escitalopram and 7,8-dihydroxyflavone(7,8-DHF)and observe the sample of male mice depression-and anxiety-like behaviors intervention and brain derived neurotrophic factor(BDNF)expression and the effect of early life stress to mental disease are discuss possible biological mechanisms,and whether early intervention can delay or prevent disease.Methods: The early life stress model was established,that is,prenatal stress combined with maternal separation.Fifty pregnant C57BL/6J mice were randomly divided into the stress group and the non-stress group.Prenatal stress: the stress group was subjected to chronic unpredictable mild stress on gestational day5-19.The process includes food and water deprivation(12 h),empty cage(12 h),wet bedding(8 h),cage tilt(angle of 45°)(12 h),flashing light(12 h),overcrowded housing(12 h),reversed light/dark cycle(24h).Maternal separation: offspring male mice in the stress group were separated from their mothers on postnatal day 2-21,and the time was from 8:00 a.m.to 12:00 a.m.,a total of 4hours.Pregnant mice and their offspring in the non-stress group were fed normally.According to the principle of random and different litter,the stress group and the non-stress group were treated with ES:10mg/kg/d,7,8-DHF:10mg/kg/d,equal volume normal saline lasted for 21 days at adolescence(PND30-50)and adulthood(PND 60-80)by intraperitoneal injection.When the mice were adults,open field test(OFT),elevated plus maze(EPM),forced swimming test(FST)were conducted to evaluate the depressionand anxiety-like behaviors.The expression of BDNF in the hippocampus(HIP),prefrontal cortex(PFC)and hypothalamus region of the mice was detected by the enzyme-linked immunosorbent assay(ELISA).Results: 1.According to the statistical analysis of the distance of OFT,it was found that ELS reduced the distance of motion of the mice,indicating that the anxiety level of the mice experiencing ELS increased.However,the intervention of ES and 7,8-dhf can increase the exercise distance of mice and alleviate this anxious state,and there is no difference in the efficacy between the two.2,The statistical analysis of the center time of OFT shows that mice who experienced early life stress showed anxious behavior with a shorter time in the center of the open field,which can be reversed by drug intervention.Both ES and DHF increased the time in the center of the open field in mice that experienced early life stress and improved their anxiety level,and there was no difference in efficacy between the two.Mice treated with drug intervention in adolescence stayed in the center area of the open field longer than the adult group in both ES level and DHF level,indicating that the effect of drug intervention in adolescence was better.3.Statistical analysis of open arm time in elevated plus maze showed that ELS reduced the residence time of mice entering open arm,and both ES and DHF intervention could increase the residence time of mice in open arm and alleviate the anxiety of mice,and there was no difference in efficacy between the two.4,According to the statistical analysis of the immobility time of forced swimming test,early life stress caused longer immobility time,indicating that ELS causes depression in mice,but drug intervention can increase the immobility time,reverse this immobility state,and improve the depressive behavior,the immobility time of adolescence is significantly shortened,indicating that the intervention in adolescent is better than that of adult at both ES level and DHF level.5,The statistical analysis of the BDNF expression in hippocampus,prefrontal cortex and hypothalamus shows that ELS make a low level of BDNF expression,ES and DHF drug intervention can improve the expression level of BDNF in different periods of different intervention,adolescent intervention can increase the expression of BDNF,indicating that the effect of adolescent intervention on BDNF expression is better than that of adult.Conclusion: Early life stress(ELS)led to depression-and anxiety-like behaviors in adult offspring of male mice,and decreased BDNF expression levels in the hippocampus(HIV),prefrontal cortex(PFC)and hypothalamus(HIP).The intervention of ES and 7,8-DHF reversed depression-and anxiety-like behaviors in adult mice and improved BDNF levels.The intervention effect of adolescence is better than that that of adulthood.