The role of DNA methylation regulating BDNF expression in depressive behavior of mice under acute restraint stress
Objective:To explore the molecular mechanism of DNA methylation regulation of BDNF expression in depressive behavior of mice by establishing a rapid depression-like behavior model in mice under 24-hour restraint stress.Methods:ICR male mice aged 8-10 weeks weighing 20-22g were used as experimental subjects.They were randomly divided into two groups,namely the normal group(Control)and the depression group(Restraint).The de-pressive behavior of mice was detected by behavior,and the mRNA and protein expression of brain-derived neurotro-phic factor(BDNF)and its receptor TrkB in hippocampus were detected.The mRNA expression of DNA methyltrans-ferase 1,DNA methyltransferase 3A,DNA methyltransferase 3B(DNMT1,DNMT3A,DNMT3B)in mice was detec-ted,and the methylation level of BDNF promoter region in mice was detected by pyrosequencing.Results:Compared with the Control group,the total distance of movement in the Restriant group was shortened(P＜0.05),the sugar water preference ratio of the Restriant group decreased(P＜0.05),the body weight recovery of the Restriant group decreased(P＜0.05),the expression of BDNF mRNA and protein in the Restriant group was decreased(P＜0.05),but there was no significant difference in the expression of TrkB protein and mRNA between the Control group and the Restriant group(P＞0.05).And compared with the Control group,the mRNA expression of DNMT3 A and DNMT3 B increased(P＜0.05),and there was no significant difference in the mRNA expression of DNMT1 between the Control group and the Restriant group.Compared with the Control group,the degree of DNA methylation in the BDNF promoter region of the Restriant group was significantly increased(P＜0.05).Conclusion:After 24 h restraint stress,mice can induce obvious depression-like behavior,which may play a role by up-regulating DNA methylation level and down-regula-ting BDNF expression.
万方数据
维普
