Agomelatine Changed the Expression and Methylation Status of Inflammatory Genes in Blood and Brain Structures of Male Wistar Rats after Chronic Mild Stress Procedure

The preclinical research conducted so far suggest that depression development may be influenced by the inflammatory pathways both at the periphery and within the central nervous system. Furthermore, inflammation is considered to be strongly connected with antidepressant treatment resistance. Thus, t...

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Main Authors: Katarzyna Bialek, Piotr Czarny, Paulina Wigner, Ewelina Synowiec, Lukasz Kolodziej, Michal Bijak, Janusz Szemraj, Mariusz Papp, Tomasz Sliwinski
Format: Article
Language:English
Published: MDPI AG 2022-08-01
Series:International Journal of Molecular Sciences
Subjects:
Online Access:https://www.mdpi.com/1422-0067/23/16/8983
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author Katarzyna Bialek
Piotr Czarny
Paulina Wigner
Ewelina Synowiec
Lukasz Kolodziej
Michal Bijak
Janusz Szemraj
Mariusz Papp
Tomasz Sliwinski
author_facet Katarzyna Bialek
Piotr Czarny
Paulina Wigner
Ewelina Synowiec
Lukasz Kolodziej
Michal Bijak
Janusz Szemraj
Mariusz Papp
Tomasz Sliwinski
author_sort Katarzyna Bialek
collection DOAJ
description The preclinical research conducted so far suggest that depression development may be influenced by the inflammatory pathways both at the periphery and within the central nervous system. Furthermore, inflammation is considered to be strongly connected with antidepressant treatment resistance. Thus, this study explores whether the chronic mild stress (CMS) procedure and agomelatine treatment induce changes in <i>TGFA</i>, <i>TGFB</i>, <i>IRF1</i>, <i>PTGS2</i> and <i>IKBKB</i> expression and methylation status in peripheral blood mononuclear cells (PBMCs) and in the brain structures of rats. Adult male Wistar rats were subjected to the CMS and further divided into matched subgroups to receive vehicle or agomelatine. 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 findings confirm that both CMS and antidepressant agomelatine treatment influenced the expression level and methylation status of the promoter region of investigated genes in PBMCs and the brain. What is more, the present study showed that response to either stress stimuli or agomelatine differed between brain structures. Concluding, our results indicate that <i>TGFA</i>, <i>TGFB</i>, <i>PTGS2</i>, <i>IRF1</i> and <i>IKBKB</i> could be associated with depression and its treatment.
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spelling doaj.art-ba894ecc180647aa9be57e07a411d4682023-12-03T13:47:43ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672022-08-012316898310.3390/ijms23168983Agomelatine Changed the Expression and Methylation Status of Inflammatory Genes in Blood and Brain Structures of Male Wistar Rats after Chronic Mild Stress ProcedureKatarzyna Bialek0Piotr Czarny1Paulina Wigner2Ewelina Synowiec3Lukasz Kolodziej4Michal Bijak5Janusz Szemraj6Mariusz Papp7Tomasz Sliwinski8Department of Medical Biochemistry, Medical University of Lodz, 92-215 Lodz, PolandDepartment of Medical Biochemistry, Medical University of Lodz, 92-215 Lodz, PolandDepartment of General Biochemistry, Faculty of Biology and Environmental Protection, University of Lodz, 90-236 Lodz, PolandLaboratory of Medical Genetics, Faculty of Biology and Environmental Protection, University of Lodz, 90-236 Lodz, PolandDepartment of Medical Biochemistry, Medical University of Lodz, 92-215 Lodz, PolandBiohazard Prevention Centre, Faculty of Biology and Environmental Protection, University of Lodz, 90-236 Lodz, PolandDepartment of Medical Biochemistry, Medical University of Lodz, 92-215 Lodz, PolandInstitute of Pharmacology, Polish Academy of Sciences, 31-343 Krakow, PolandLaboratory of Medical Genetics, Faculty of Biology and Environmental Protection, University of Lodz, 90-236 Lodz, PolandThe preclinical research conducted so far suggest that depression development may be influenced by the inflammatory pathways both at the periphery and within the central nervous system. Furthermore, inflammation is considered to be strongly connected with antidepressant treatment resistance. Thus, this study explores whether the chronic mild stress (CMS) procedure and agomelatine treatment induce changes in <i>TGFA</i>, <i>TGFB</i>, <i>IRF1</i>, <i>PTGS2</i> and <i>IKBKB</i> expression and methylation status in peripheral blood mononuclear cells (PBMCs) and in the brain structures of rats. Adult male Wistar rats were subjected to the CMS and further divided into matched subgroups to receive vehicle or agomelatine. 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 findings confirm that both CMS and antidepressant agomelatine treatment influenced the expression level and methylation status of the promoter region of investigated genes in PBMCs and the brain. What is more, the present study showed that response to either stress stimuli or agomelatine differed between brain structures. Concluding, our results indicate that <i>TGFA</i>, <i>TGFB</i>, <i>PTGS2</i>, <i>IRF1</i> and <i>IKBKB</i> could be associated with depression and its treatment.https://www.mdpi.com/1422-0067/23/16/8983depressionchronic mild stressagomelatineinflammationexpressionmethylation
spellingShingle Katarzyna Bialek
Piotr Czarny
Paulina Wigner
Ewelina Synowiec
Lukasz Kolodziej
Michal Bijak
Janusz Szemraj
Mariusz Papp
Tomasz Sliwinski
Agomelatine Changed the Expression and Methylation Status of Inflammatory Genes in Blood and Brain Structures of Male Wistar Rats after Chronic Mild Stress Procedure
International Journal of Molecular Sciences
depression
chronic mild stress
agomelatine
inflammation
expression
methylation
title Agomelatine Changed the Expression and Methylation Status of Inflammatory Genes in Blood and Brain Structures of Male Wistar Rats after Chronic Mild Stress Procedure
title_full Agomelatine Changed the Expression and Methylation Status of Inflammatory Genes in Blood and Brain Structures of Male Wistar Rats after Chronic Mild Stress Procedure
title_fullStr Agomelatine Changed the Expression and Methylation Status of Inflammatory Genes in Blood and Brain Structures of Male Wistar Rats after Chronic Mild Stress Procedure
title_full_unstemmed Agomelatine Changed the Expression and Methylation Status of Inflammatory Genes in Blood and Brain Structures of Male Wistar Rats after Chronic Mild Stress Procedure
title_short Agomelatine Changed the Expression and Methylation Status of Inflammatory Genes in Blood and Brain Structures of Male Wistar Rats after Chronic Mild Stress Procedure
title_sort agomelatine changed the expression and methylation status of inflammatory genes in blood and brain structures of male wistar rats after chronic mild stress procedure
topic depression
chronic mild stress
agomelatine
inflammation
expression
methylation
url https://www.mdpi.com/1422-0067/23/16/8983
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