Effects Of Chronic Restraint Stress During Adulthood And Adolescence Of Male Mice On Anxiety-like Behavior Of Offspring

With the development of the society and the progress of science and technology,people's life rhythm is faster,and the psychological pressure is bigger.Psychological stress for a long time is increased vulnerability to psychiatric diseases such as anxiety and depression.Although studies suggested that both gestational stress and neonatal nurture caused psychological alterations in the progeny,whether the adolescent and adult life events would cause offspring behavioral changes is unknown.Furthermore,researches are limited on whether the context-dependent epigenetic modifications made in adults could be immediately incorporated into the germ line to manifest in the progeny and then be passed on to the next generation.Here,we tested whether adolescent and adult restraint stress would cause offspring behavioral alterations by acting on the developing gametes and whether the alterations could be inherited.So we used this experimental model to design a series of research on the chronic restraint stress affecting the offspring anxiety behavior.In this study,KunMing male adolescent and adult mice were used,and chronic(8h/d,60days)restraint stress were used as psychological stress model,to investigate the effects of chronic psychological stress on the offspring's anxiety behavior(behavioral,hormone and molecular level).To produce the first generation,Stressed mice were paired with control non-defeated female mice.The F1 mice obtained from male adult mice restrained for 60 days were mated with control mice or with each other to produce the second generation.The results are summarized as follows:1.Both the male and female F1 offspring obtained from male adult mice restrained for 60 days spent more time in the open arms of EPM.In addition,the open arms entries of F1 were more than control mice.So F1 offspring obtained from male adult mice restrained for 60 days showed significantly reduced levels of anxiety-like behavior.2.Both the male and female F1 offspring obtained from male adult mice restrained for 60 days spent more time in the central area of OFT.Whatever the central area entries and CD/TD were both significant different from control mice.The results indicated that F1 offspring obtained from male adult mice restrained for 60 days showed significantly reduced levels of anxiety-like behavior.3.The level of serum cortisol of the F1 offspring obtained from male adult mice restrained for 60 days after EPM is lower than the control mice significantly.The results indicated that the anxiety-like behavior of F1 offspring obtained from male adult mice restrained for 60 days was significant reduced in the level of hormone.4.The expression of GR and BDNF in the hippocampal of F1 offspring of chronic restraint stress male adult mice 60 days is more than the control mice significantly.The results indicated that the anxiety-like behavior of F1 offspring of chronic restraint stress male adult mice 60 days was significant reduced in the level of molecular.5.Both the male and female F1 offspring obtained from male adolescent mice restrained for 60 days also showed significantly reduced levels of anxiety-like behavior and serum cortisol,with increased expression of hippocampal glucocorticoid receptor(GR)and brain-derived neurotrophic factor(BDNF)compared to offspring from matings between unstressed parents.6.Both the male and female F1 offspring obtained from both parents restrained for 60 days showed significantly reduced levels of anxiety-like behavior and serum cortisol and increased expression of hippocampal glucocorticoid receptor(GR)and brain-derived neurotrophic factor(BDNF)compared to F1 offspring obtained from male adult mice restrained for 60 days with a tendency of lower.7.When the F1 mice obtained from male adult mice restrained for 60 days were mated with control mice or with each other,both the female and male F2 offspring showed significantly reduced anxiety-like behavior and cortisol level with increased GR and BDNF expression compared to F2 offspring produced by the control F1 mothers and fathers.And both the female and male F2 “homozygous” offspring produced by the stressed F1 mothers and fathers showed reduced anxiety-like behavior and cortisol level with increased GR and BDNF expression compared to F2“ heterozygous”offspring produced by the stressed F1 mothers or fathers with a tendency of lower.Together,the results showed for the first time that adolescent and adult restraint stress reduced offspring's stress response.F1 offspring obtained from both parents restrained for 60 days showed significantly reduced levels of anxiety-like behavior with a tendency of lower.Furthermore male mice restraint stress might reduce offspring's anxiety-like behavior by acting on the developing gametes and the epigenetic modifications made were inheritable.