Recent studies imply that there is a tight association between epigenetics and a molecular mechanism of major depressive disorder (MDD). Epigenetic modifications, i.e., DNA methylation, post-translational histone modification and interference of microRNA (miRNA) or long non-coding RNA (lncRNA), are able to influence the severity of the disease and the outcome of the therapy. This article summarizes the most recent literature data on this topic, i.e., usage of histone deacetylases as therapeutic agents with an antidepressant effect and miRNAs or lncRNAs as markers of depression. Due to the noteworthy potential of the role of epigenetics in MDD diagnostics and therapy, we have gathered the most relevant data in this area.

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 Sod1, Sod2, Gpx1, Gpx4, Cat, Nos1, and Nos2 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. Gpx1, Gpx4, and Sod2 expression in the PBMCs and Sod1 and Sod2 expression in the brain were reduced in the stressed group after agomelatine administration. CMS caused an increase in the methylation of the third Gpx4 promoter in peripheral blood mononuclear cells and Gpx1 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.

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Purpose Oxidative stress plays an important role in the pathogenesis of age‐related macular degeneration (AMD), but the exact mechanism of the influence of the stress is not completely clear. The stress can affect both neural retina and retinal pigment epithelium (RPE) cells The purpose of our study was to evaluate changes in some mitochondrial properties and autophagy in the response of RPE cells to oxidative stress. Methods Retinal pigment epithelium ARPE‐19 cells were challenged with 200 mM H2O2 for 2 h. Mitochondrial ROS (mtROS) were assessed by the MitoSOX probe, mitochondrial membrane potential (MMP) with JC‐1, the activity of the complex I of the mitochondrial respiratory chain with MitoCheck. To assess autophagy cells were transfected with the pBABE‐puro mCherry‐EGFP‐LC3B plasmid and autophagic flux was evaluated with confocal fluorescent microscopy; expression of the LC3‐I and LC3‐II proteins were quantified by immunoblotting. Results Hydrogen peroxide induced an increase in mtROS and decrease in MMP in ARPE‐19 cells as well as it inhibited the activity of the complex I. Furthermore, an increase in the LC3‐II/LC3‐I ratio and an increased number of autophagolysosomes was observed in ARPE‐19 cells challenged with hydrogen peroxide. Conclusion Oxidative stress induces detrimental changes in mitochondria of RPE cells that can respond to these changes by increased autophagy, confirming that mitochondrial homeostasis and autophagy may be important in AMD pathogenesis. This work was supported by National Science Centre, Poland grant number 2017/27/B/NZ3/00872.

Preclinical studies conducted to date suggest that depression could be elicited by the elevated expression of proinflammatory molecules: these play a key role in the mediation of neurochemical, neuroendocrine and behavioral changes. Thus, this study investigates the effect of chronic mild stress (CMS) and administration of venlafaxine (SSRI) on the expression and methylation status of new target inflammatory genes: TGFA, TGFB, IRF1, PTGS2 and IKBKB, in peripheral blood mononuclear cells (PMBCs) and in selected brain structures of rats. Adult male Wistar rats were subjected to the CMS and further divided into matched subgroups to receive vehicle or venlafaxine. TaqMan gene expression assay and methylation-sensitive high-resolution melting (MS-HRM) were used to evaluate the expression of the genes and the methylation status of their promoters, respectively. Our results indicate that both CMS and chronic treatment with venlafaxine were associated with changes in expression of the studied genes and their promoter methylation status in PMBCs and the brain. Moreover, the effect of antidepressant administration clearly differed between brain structures. Summarizing, our results confirm at least a partial association between TGFA, TGFB, IRF1, PTGS2 and IKBKB and depressive disorders.