MGluR3 DNA Methylation Mediated The Depression-like Behavior Of Prenatally Stressed Offspring Rats

In recent years,glutamate as a classical neurotransmitter has been found to play an important role in the pathogenesis of depression,but the underlying mechanism has not been established yet.Studies have shown that mGluR2 and mGluR3 play a role in depression and other mood disorders.The present study found that the protein and m RNA expression of mGluR2 and mGluR3 in the hippocampal and cortical regions of PS mice was decreased.Recent studies have shown that the pathogenesis of mental and emotional disorders may be related to epigenetic mechanisms.To determine the possible involvement of epigenetic mechanisms in prenatally stressed depression-like behaviors,we studied the DNA methylation levels of mGluR2 and mGluR3 in the hippocampus and frontal cortex of PS offspring.5-aza,a common DNA methylase inhibitor,can reverse DNA methylation and increase the level of DNA transcription.Male rat offspring were allocated into the following 4 groups: C(control group);PS;PS+5-aza D and PS+ saline.RT-PCR and blotting were used to determine the expression of mGluR2 and mGluR3 in the hippocampus and frontal cortex of PS offspring.Levels of mGlu R-2 and-3 DNA methylation was measures with bisulphite sequencing.1.In the open field experiment,the central stay time of the PS group,the number of rest times and the total number of the total squares were significantly reduced compared with that of the CON group,while the fecal particles of each group were not significantly different;forced swimming test manifested prenatal stress prolonged the immobility time in male offspring compared with CON group;sucrose preference test indicated that prenatal stress increased the percentage of sucrose preference in male offspring compared with CON group.2.Western Blotting and PCR results shown the expression levels of mGluR2 and mGluR3 in hippocampus and prefrontal cortex was decreased.3.Results of 5-aza D intraperitoneal injection in PS mice showed that 5-aza D could reverse the expression of mGluR2 and mGluR3 mRNA and protein in the hippocampus and cortex of PS mice.4.The results of sulfite sequencing showed a significantly increase in DNA methylation levels in mGluR2 and mGluR3 promoter regions in the hippocampal and cortical regions of the PS.Conclusion 1.PS decreased the level of mGluR2 and mGluR3 expression,which was associated with increased DNA methylation at the promoter region of the genes in the hippocampus.2.These results suggested that mGluR2 and 3 DNA methylation modification is involved in depression-like behavior in prenatally stressed offspring rats.