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Article

The Effect of Chronic Mild Stress and Escitalopram on the Expression and Methylation Levels of Genes Involved in the Oxidative and Nitrosative Stresses as Well as Tryptophan Catabolites Pathway in the Blood and Brain Structures

1
Laboratory of Medical Genetics, Faculty of Biology and Environmental Protection, University of Lodz, 90-136 Lodz, Poland
2
Department of Cytobiochemistry, Faculty of Biology and Environmental Protection, University of Lodz, 90-136 Lodz, Poland
3
Department of Medical Biochemistry, Medical University of Lodz, 90-647 Lodz, Poland
4
Biohazard Prevention Centre, Faculty of Biology and Environmental Protection, University of Lodz, 90-136 Lodz, Poland
5
Institute of Pharmacology, Polish Academy of Sciences, 31-343 Krakow, Poland
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2021, 22(1), 10; https://doi.org/10.3390/ijms22010010
Received: 21 October 2020 / Revised: 2 December 2020 / Accepted: 18 December 2020 / Published: 22 December 2020
(This article belongs to the Special Issue Tryptophan in Nutrition and Health)
Previous studies suggest that depression may be associated with reactive oxygen species overproduction and disorders of the tryptophan catabolites pathway. Moreover, one-third of patients do not respond to conventional pharmacotherapy. Therefore, the study investigates the molecular effect of escitalopram on the expression of Cat, Gpx1/4, Nos1/2, Tph1/2, Ido1, Kmo, and Kynu and promoter methylation in the hippocampus, amygdala, cerebral cortex, and blood of rats exposed to CMS (chronic mild stress). The animals were exposed to CMS for two or seven weeks followed by escitalopram treatment for five weeks. The mRNA and protein expression of the genes were analysed using the TaqMan Gene Expression Assay and Western blotting, while the methylation was determined using methylation-sensitive high-resolution melting. The CMS caused an increase of Gpx1 and Nos1 mRNA expression in the hippocampus, which was normalised by escitalopram administration. Moreover, Tph1 and Tph2 mRNA expression in the cerebral cortex was increased in stressed rats after escitalopram therapy. The methylation status of the Cat promoter was decreased in the hippocampus and cerebral cortex of the rats after escitalopram therapy. The Gpx4 protein levels were decreased following escitalopram compared to the stressed/saline group. It appears that CMS and escitalopram influence the expression and methylation of the studied genes. View Full-Text
Keywords: depression; chronic mild stress; oxidative stress; tryptophan catabolites pathway; methylation; expression; escitalopram depression; chronic mild stress; oxidative stress; tryptophan catabolites pathway; methylation; expression; escitalopram
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MDPI and ACS Style

Wigner, P.; Synowiec, E.; Jóźwiak, P.; Czarny, P.; Bijak, M.; Białek, K.; Szemraj, J.; Gruca, P.; Papp, M.; Śliwiński, T. The Effect of Chronic Mild Stress and Escitalopram on the Expression and Methylation Levels of Genes Involved in the Oxidative and Nitrosative Stresses as Well as Tryptophan Catabolites Pathway in the Blood and Brain Structures. Int. J. Mol. Sci. 2021, 22, 10. https://doi.org/10.3390/ijms22010010

AMA Style

Wigner P, Synowiec E, Jóźwiak P, Czarny P, Bijak M, Białek K, Szemraj J, Gruca P, Papp M, Śliwiński T. The Effect of Chronic Mild Stress and Escitalopram on the Expression and Methylation Levels of Genes Involved in the Oxidative and Nitrosative Stresses as Well as Tryptophan Catabolites Pathway in the Blood and Brain Structures. International Journal of Molecular Sciences. 2021; 22(1):10. https://doi.org/10.3390/ijms22010010

Chicago/Turabian Style

Wigner, Paulina, Ewelina Synowiec, Paweł Jóźwiak, Piotr Czarny, Michał Bijak, Katarzyna Białek, Janusz Szemraj, Piotr Gruca, Mariusz Papp, and Tomasz Śliwiński. 2021. "The Effect of Chronic Mild Stress and Escitalopram on the Expression and Methylation Levels of Genes Involved in the Oxidative and Nitrosative Stresses as Well as Tryptophan Catabolites Pathway in the Blood and Brain Structures" International Journal of Molecular Sciences 22, no. 1: 10. https://doi.org/10.3390/ijms22010010

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