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Open AccessArticle

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

1
Laboratory of Medical Genetics, Faculty of Biology and Environmental Protection, University of Lodz, 90-236 Lodz, Poland
2
Department of Cytobiochemistry, Faculty of Biology and Environmental Protection, University of Lodz, 90-236 Lodz, Poland
3
Department of Medical Biochemistry, Medical University of Lodz, 92-216 Lodz, Poland
4
Department of General Biochemistry, Faculty of Biology and Environmental Protection, University of Lodz, 90-236 Lodz, Poland
5
Polish Academy of Sciences, Institute of Pharmacology, 31-343 Krakow, Poland
*
Author to whom correspondence should be addressed.
Genes 2020, 11(6), 644; https://doi.org/10.3390/genes11060644
Received: 8 May 2020 / Revised: 5 June 2020 / Accepted: 9 June 2020 / Published: 11 June 2020
(This article belongs to the Section Molecular Genetics and Genomics)
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. View Full-Text
Keywords: chronic mild stress model; agomelatine; oxidative stress; gene expression and methylation chronic mild stress model; agomelatine; oxidative stress; gene expression and methylation
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MDPI and ACS Style

Wigner, P.; Synowiec, E.; Jóźwiak, P.; Czarny, P.; Bijak, M.; Barszczewska, G.; Białek, K.; Szemraj, J.; Gruca, P.; Papp, M.; Śliwiński, T. The Changes of Expression and Methylation of Genes Involved in Oxidative Stress in Course of Chronic Mild Stress and Antidepressant Therapy with Agomelatine. Genes 2020, 11, 644.

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