The Impact And Mechanism Of MGluR1 And MGluR5 Methylated In Different Brain Regions On Depression-like Behavior In Prenatal Stress Offspring Rats

Background: Increasing number of epidemiological investigations and animal models research suggest that prenatal stress(PS)could cause depression-like behavior in the offspring,which is sex-specific.However,the underlying mechanisms remain to be elucidated.This study is to investigate the promoter methylation of mGluR1 and mGluR5 gene modification on PS induced depression-like behavior in offspring rats.Purposes: This research adopts the restraint stress model,DNA methyltransferase inhibitor 5-azaD(5-aza-2’-deoxycytidine,5-azaD,decitabine,DNA methyltransferase inhibitor)is given at the same time,detection of 1 month old offspring rats in the hippocampus and prefrontal cortex of mGluRs(mGluR1 and mGluR5)and the changes in the promoter region of DNA methylation,and the difference between male and female offspring rats to explore the mechanism in offspring in effect of prenatal stress of epigenetic inheritance in the depressive behaviors,provide experimental and theoretical basis for future theoretical research.Methods: In this experiment,Virgin Sprague-Dawley(SD)rats were provided by the Experimental Animal Centre of Xi’an Jiao Tong University School.These animals were housed with free access to food and water at a constant temperature of 20 ± 2 °C,under a 12 h light/dark cycle(lights were on at 8:00 a.m.).Female rats(weighing 230–250 g)were placed overnight with adult male rats(weighing 280–300 g)for mating(rate of 3:1).The vaginal smear was examined on the following morning.The day on which the smear was positive for the sperm detection was determined as the embryonic day 0.Then the pregnant rats were separately housed.All animals were treated in accordance with the guidelines of the Centre for the Humane Treatment of Animals.Moreover,attempts were also made as a means to minimize the number of animals used.Animal behavior was assessed by the sucrose preference test(SPT),forced swimming test(FST),and open field test(OFT).The mRNA and protein expression levels of mGluR1 and mGluR5 in the hippocampus of offspring were detected with quantitative real-time PCR and Western blot analysis,respectively.The promoter methylation in the hippocampus of mGluR1 and mGluR5 OR were also analyzed.Results:(1)the level of depressive behavior of rats in the exciton generation before birth was significantly higher than that in the control group,while the depression like behavior of the offspring of the offspring of the offspring of 5-azaD was significantly lower than that in the stress group,and there was no significant difference between the female and the male and the male offspring.(2)the expression of mRNA and protein of mGluR1 and mGluR5 in the hippocampus and prefrontal cortex of the exciton generation rats was significantly higher than that in the control group,and there was a gender difference between the male and the male offspring(p<0.05).(3)the methylation expression in the DNA promoter region of the hippocampus and prefrontal cortex in the exciton generation rats was significantly higher than that in the control group before production,and there was a gender difference between the female and the male and the male offspring(p<0.05).Conclusion: The results of this study found that PS could induce depression and anxiety like behavior in rats,probably due to the increase of methylation in the promoter region of mGluR1 and mGluR5.The antidepressant effect of 5-azaD is accompanied by the decrease of mRNA expression and protein expression in mGluR1 and mGluR5 and the decrease of DNA methylation in the promoter region.It is suggested that DNA methylation modification may be an important epigenetic component involved in the pathogenesis of depression.