The Changes of Expression and Methylation of Genes Involved in Oxidative Stress in Course of Chronic Mild Stress and Antidepressant Therapy with Agomelatine.

Preclinical studies conducted so far suggest that oxidative stress processes may be associated with the mechanism of depression development. This study shows the effects of chronic administration of agomelatine on expression and the methylation status of , , , , , and in the brain stricture and blood in the chronic mild stress (CMS) animal model of depression. The animals were exposed to the CMS procedure and treatment with agomelatine (10 mg/kg/day, IP) for five weeks and then were sacrificed. TaqMan Gene Expression Assay, Western blot, and methylation-sensitive high-resolution melting techniques were used to evaluate mRNA and protein expression of the genes, and the methylation status of their promoters. , and expression in the PBMCs and and expression in the brain were reduced in the stressed group after agomelatine administration. CMS caused an increase in the methylation of the third promoter in peripheral blood mononuclear cells and promoter in the cerebral cortex. Additionally, stressed rats treated with agomelatine displayed a significantly lower Gpx4 level in the hypothalamus. The results confirm the hypothesis that the CMS procedure and agomelatine administration change the expression level and methylation status of the promoter region of genes involved in oxidative and nitrosative stress.