Expression Levels Of Lysine Methyltransferase And Lysine Demethylase In Hippocampal CA1 Region Of Rats With Depression-Like Behavior

Objective:Depression is a common mental illness that has become an important factor in the global burden of disease.Ventral hippocampal CA1 region mediates neuroendocrine,autonomic and emotional behavior activities,and is closely related to the occurrence and development of depression.Brain-derived neurotrophic factor(BDNF)is highly expressed in the hippocampus,and regulates the structure and function of hippocampal neurons.BDNF expression is regulated by histone methylation,which is a dynamic process mediated by histone lysine methyltransferases(KMTs)and histone lysine demethylases(KDMs).In this study,the expression of KMTs and KDMs in hippocampal CA1 region of rats with depression-like behavior was studied,and their binding with different promoter regions of Bdnf gene was explored and analyzed.Purpose:The rats with depression-like behavior were prepared to observe the change level of Bdnf genome protein methylation modification enzyme in hippocampus CA1 region and their binding with different promoter regions.Methods:1.rats with depression-like behavior was prepared by using Corticosterone(CORT)orally and chronically: Twenty SPF male SD rats(200-250 g)were fed in12/12 h light/dark conditions with sufficient food and water.Rats were adaptively fed for 1 week and divided into normal group and CORT group according to body weight and basic sugar water consumption.The rats in the CORT group were fed in single cages.The concentration of CORT was 50 μg/ml in the first 2 weeks,and then 50%initial CORT concentration was administered for 3 days,and 25% initial CORT concentration was administered for the last 4 days to restore normal drinking water and continue the experiment.2.Evaluation of depressive behavior in rats: The depression behavior of rats was evaluated by weight change,sugar water preference experiment,open field experiment,elevated cross maze experiment and forced swimming experiment.3.The expression levels of different subtypes of KMTs and KDMs in hippocampal ventral CA1 neurons were detected by Western blot(WB).4.Chromatin Immunoprecipitation(Ch IP)was used to detect the binding of different promoter regions of Bdnf gene to KDMs and KMTs.Results:1.There was no significant difference between the CORT group and the normal group in the first two weeks of the experiment,but it was significantly lower than the normal group in the third week,with statistical significance(P < 0.05).2.In open field test,the number of standing,the total distance of horizontal movement and the residence time in the central area of the rats in the CORT group decreased after administration,and the residence time in the corner was prolonged.Compared with before administration and the control group,the difference was significant(P < 0.05),while the difference in the control group was not statistically significant.3.In the experiment of sucrose preference test,after administration,the sugar water preference of rats in the CORT group decreased,which was significantly different from that before administration and the control group(P < 0.05),and the difference in the control group was not statistically significant.4.The elevated plus maze test showed that the CORT group had a shortened residence time in the open arm and a prolonged residence time in the closed arm.Compared with before administration and the control group,the difference was significant(P < 0.05),and there was no difference in the control group5.In the forced swimming test,the floating immobility time of rats in the CORT group was prolonged after administration,which was significantly different from that before administration and the control group(P < 0.05),and the difference in the control group was not statistically significant.6.WB results showed that,Compared with the normal group,there was no significant difference in the expression levels of KMT2 A,KMT3A,KMT6,KDM1,KDM3 A and KDM6 A in the hippocampal CA1 region of rats with depression-like behavior..However,the expression levels of KMT1 D and KDM2 A decreased,with statistical difference(P < 0.05).7.Ch IP results showed that the binding levels of KMT1 D and Bdnf gene promoters I,II and VI in hippocampal CA1 region of rats with depression-like behavior decreased(P < 0.05)and there was no significant change in the binding level with promoter IV The binding level of KDM2 A to promoter VI increased(P < 0.05),and there was no significant change in the binding level of KDM2 A to promoters I,II and IV.Conclusions:1.The expressions of KMT1 D and KDM2 A in the ventral CA1 region of hippocampus of rats with depression-like behavior were significantly decreased,while the expressions of KMT2 A,KMT3A,KMT6,KDM1 A,KDM6A and KDM3 A were not significantly changed.2.The binding levels of KMT1 D and Bdnf gene promoters with I,II and VI decreased in hippocampal CA1 region of rats with depression-like behavior,while the binding levels with promoter IV had no significant change;The binding level of KDM2 A with promoter VI increased,but the binding level of KDM2 A with promoter I,II,IV had no significant change.