scholarly journals 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 ◽  
Vol 11 (6) ◽  
pp. 644
Author(s):  
Paulina Wigner ◽  
Ewelina Synowiec ◽  
Paweł Jóźwiak ◽  
Piotr Czarny ◽  
Michał Bijak ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Nitrosative Stress ◽  
Mononuclear Cells ◽  
Methylation Status ◽  
Chronic Mild Stress ◽  
Mild Stress ◽  
Oxidative And Nitrosative Stress ◽  
Peripheral Blood Mononuclear ◽  
Taqman Gene Expression Assay ◽  
The Brain

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.

scholarly journals The Impact of Chronic Mild Stress and Agomelatine Treatment on the Expression Level and Methylation Status of Genes Involved in Tryptophan Catabolic Pathway in PBMCs and Brain Structures

Genes ◽  
2020 ◽  
Vol 11 (9) ◽  
pp. 1093
Author(s):  
Paulina Wigner ◽  
Ewelina Synowiec ◽  
Paweł Jóźwiak ◽  
Piotr Czarny ◽  
Katarzyna Białek ◽  
...  
Keyword(s):  
Protein Expression ◽  
Messenger Rna ◽  
Mononuclear Cells ◽  
Methylation Status ◽  
Chronic Mild Stress ◽  
Brain Structures ◽  
Mild Stress ◽  
Catabolic Pathway ◽  
Peripheral Blood Mononuclear ◽  
The Impact

Depression is the serious mental disorder. Previous studies suggest that the development mechanism of depression may be associated with disorders of the tryptophan catabolic pathway (TRYCAT). Thus, this study investigates the effect of agomelatine treatment on the expression and methylation status of genes involved in TRYCAT in the brain and blood of rats exposed to a chronic mild stress (CMS). Separate groups of rats were exposed to CMS for two or seven weeks; the second group received vehicle or agomelatine for five weeks. After completion of both stress conditions and treatment, the expression levels of messenger RNA (mRNA) and protein, as well as the methylation status of promoters, were measured in peripheral blood mononuclear cells (PBMCs) and in brain structures with the use of TaqMan Gene Expression Assay, Western blot, and methylation-sensitive high-resolution melting techniques. In PBMCs, Kmo mRNA expression increased in the group after CMS, while this effect was normalized by agomelatine therapy. In brain, KatI and KatII expression changed following CMS exposure. Moreover, CMS decreased the methylation status of the second Tdo2 promoter in the amygdala. Protein expression of Tph1, Tph2, Ido1, and KatII changed in the group after CMS and agomelatine administration, most prominently in the basal ganglia, cerebral cortex, hippocampus, and amygdala. The results indicate that CMS and agomelatine affect the mRNA and protein expression, as well as the methylation of promoters of genes involved in the tryptophan catabolic pathway.

scholarly journals Chronic Mild Stress and Venlafaxine Treatment Were Associated with Altered Expression Level and Methylation Status of New Candidate Inflammatory Genes in PBMCs and Brain Structures of Wistar Rats

Genes ◽  
2021 ◽  
Vol 12 (5) ◽  
pp. 667
Author(s):  
Katarzyna Bialek ◽  
Piotr Czarny ◽  
Paulina Wigner ◽  
Ewelina Synowiec ◽  
Gabriela Barszczewska ◽  
...  
Keyword(s):  
Wistar Rats ◽  
Depressive Disorders ◽  
Mononuclear Cells ◽  
Methylation Status ◽  
Chronic Mild Stress ◽  
Brain Structures ◽  
Mild Stress ◽  
Peripheral Blood Mononuclear ◽  
Altered Expression ◽  
Inflammatory Genes

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.

scholarly journals Effects of venlafaxine on the expression level and methylation status of genes involved in oxidative stress in rats exposed to a chronic mild stress

2020 ◽  
Vol 24 (10) ◽  
pp. 5675-5694 ◽  
Author(s):  
Paulina Wigner ◽  
Ewelina Synowiec ◽  
Piotr Czarny ◽  
Michal Bijak ◽  
Paweł Jóźwiak ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Methylation Status ◽  
Chronic Mild Stress ◽  
Expression Level ◽  
Mild Stress

Increased oxidative stress in submitochondrial particles into the brain of rats submitted to the chronic mild stress paradigm

2009 ◽  
Vol 43 (9) ◽  
pp. 864-869 ◽  
Author(s):  
Giancarlo Lucca ◽  
Clarissa M. Comim ◽  
Samira S. Valvassori ◽  
Gislaine Z. Réus ◽  
Francieli Vuolo ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Chronic Mild Stress ◽  
Mild Stress ◽  
Submitochondrial Particles ◽  
The Brain

scholarly journals Oxidative stress and post-stroke depression

2018 ◽  
Vol 16 (3) ◽  
pp. 249-253 ◽  
Author(s):  
D. Komsiyska
Keyword(s):  
Oxidative Stress ◽  
Free Radical ◽  
Nitrosative Stress ◽  
Multifactorial Disease ◽  
Oxygen Utilization ◽  
Oxidative And Nitrosative Stress ◽  
Post Stroke ◽  
Mental Diseases ◽  
Post Stroke Depression ◽  
The Brain

The topic of post-stroke depression etiology is reviewed in two main approaches. Some suggest that post-stroke depression is caused by the brain damage itself. On the contrary, others assume that this is a psychologic response to injuries or loss. Many discoveries can be examined as evidence for both the physiological and psychosocial mechanism of post-stroke depression. The two methods are not self-excluding, but instead describe post-stroke depression as a complex and multifactorial disease with interactions between the physiological and environmental factor. One hypothesis about depression occurrence is the inflammatory, oxidative and nitrosative stress (IO&NS) depression theory. Oxidative stress mechanisms are implied in the pathogenesis of mental diseases. The brain is considered particularly vulnerable to oxidative damage, due to its relatively high oxygen utilization and thus generation of free radical subordinate products, its modest antioxidant protections and its lipid-rich resistance.

Aldosteronism: an immunostimulatory state precedes proinflammatory/fibrogenic cardiac phenotype

2003 ◽  
Vol 285 (2) ◽  
pp. H813-H821 ◽  
Author(s):  
Ivan C. Gerling ◽  
Yao Sun ◽  
Robert A. Ahokas ◽  
Linus A. Wodi ◽  
Syamal K. Bhattacharya ◽  
...  
Keyword(s):  
Cardiac Tissue ◽  
Nitrosative Stress ◽  
Mononuclear Cells ◽  
Inflammatory Cells ◽  
Vascular Lesions ◽  
Oxidative And Nitrosative Stress ◽  
Peripheral Blood Mononuclear ◽  
Cardiac Phenotype ◽  
And Gender ◽  
The Right

Chronic inappropriate (relative to dietary Na+intake) elevations in circulating aldosterone (ALDO), termed aldosteronism, are associated with remodeling of intramural arteries of the right and left heart. Lesions appear at week 4 of treatment with ALDO and 1% dietary NaCl in uninephrectomized rats (ALDOST) and include invading monocytes, macrophages and lymphocytes with intracellular evidence of oxidative and nitrosative stress, myofibroblasts, and perivascular fibrosis. In this study, we tested the hypothesis that an immunostimulatory state with activated circulating peripheral blood mononuclear cells (PBMCs) precedes this proinflammatory and profibrogenic cardiac phenotype and is initiated by reduction in the cytosolic free Mg2+concentration ([Mg2+]i). At 1 and 4 wk of ALDOST (preclinical and clinical stages, respectively), we monitored serum Mg2+, PBMC [Mg2+]iand cytosolic free [Ca2+] (via fluorimetry), and expressed genes (via microchip array) as well as markers of oxidative and nitrosative stress in plasma [α1-antiproteinase activity (α1-AP)] and cardiac tissue (immunohistochemical detection of gp91phoxsubunit of NADPH oxidase and 3-nitrotyrosine). Age- and gender-matched unoperated and untreated (UO) rats and uninephrectomized salt-treated (UN) rats served as controls. Serum [Mg2+] was unchanged by ALDOST. In contrast with UO and UN, [Mg2+]iand plasma α1-AP were each reduced ( P < 0.05) at weeks 1 and 4. The decline in PBMC [Mg2+]iwas accompanied by Ca2+loading. Differential (twofold and higher) expression (up- and downregulation) in PBMC transcriptomes was present at week 1 and progressed at week 4. Involved were genes for the α1-isoform of Na+-K+-ATPase, the ATP-dependent Ca2+pump, antioxidant reserves, inducible nitric oxide synthase, and PBMC activation with autoimmune responses. Expression of 3-nitrotyrosine and activation of gp91phoxwere seen in inflammatory cells that invaded intramural arteries. Thus early in aldosteronism (preclinical stage), an immunostimulatory state featuring activated circulating PBMCs with reduced ionized [Mg2+]iand oxidative and nitrosative stress precedes and may even predispose to coronary vascular lesions that first appear at week 4.

scholarly journals 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

2020 ◽  
Vol 22 (1) ◽  
pp. 10
Author(s):  
Paulina Wigner ◽  
Ewelina Synowiec ◽  
Paweł Jóźwiak ◽  
Piotr Czarny ◽  
Michał Bijak ◽  
...  
Keyword(s):  
Cerebral Cortex ◽  
Mrna Expression ◽  
Methylation Status ◽  
Chronic Mild Stress ◽  
Brain Structures ◽  
Saline Group ◽  
Mild Stress ◽  
Taqman Gene Expression Assay ◽  
Protein Levels ◽  
Tryptophan Catabolites

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.

Behavior and oxidative stress parameters in rats subjected to the animal's models induced by chronic mild stress and 6-hydroxydopamine

2021 ◽  
Vol 406 ◽  
pp. 113226
Author(s):  
Talita Tuon ◽  
Sandra S. Meirelles ◽  
Airam B. de Moura ◽  
Thayse Rosa ◽  
Laura A. Borba ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Chronic Mild Stress ◽  
Mild Stress ◽  
Oxidative Stress Parameters ◽  
6 Hydroxydopamine ◽  
And Oxidative Stress ◽  
Stress Parameters

scholarly journals The 2′-O-methylation status of a single guanosine controls transfer RNA–mediated Toll-like receptor 7 activation or inhibition

2012 ◽  
Vol 209 (2) ◽  
pp. 235-241 ◽  
Author(s):  
Stefanie Jöckel ◽  
Gernot Nees ◽  
Romy Sommer ◽  
Yang Zhao ◽  
Dmitry Cherkasov ◽  
...  
Keyword(s):  
Influenza A ◽  
Mononuclear Cells ◽  
Human Peripheral Blood ◽  
Thermus Thermophilus ◽  
Methylation Status ◽  
Transfer Rna ◽  
Type I ◽  
Peripheral Blood Mononuclear ◽  
Molecular Pattern

Foreign RNA serves as pathogen-associated molecular pattern (PAMP) and is a potent immune stimulator for innate immune receptors. However, the role of single bacterial RNA species in immune activation has not been characterized in detail. We analyzed the immunostimulatory potential of transfer RNA (tRNA) from different bacteria. Interestingly, bacterial tRNA induced type I interferon (IFN) and inflammatory cytokines in mouse dendritic cells (DCs) and human peripheral blood mononuclear cells (PBMCs). Cytokine production was TLR7 dependent because TLR7-deficient mouse DCs did not respond and TLR7 inhibitory oligonucleotides inhibited tRNA-mediated activation. However, not all bacterial tRNA induced IFN-α because tRNA from Escherichia coli Nissle 1917 and Thermus thermophilus were non-immunostimulatory. Of note, tRNA from an E. coli knockout strain for tRNA (Gm18)-2′-O-methyltransferase (trmH) regained immunostimulatory potential. Additionally, in vitro methylation of this immunostimulatory Gm18-negative tRNA with recombinant trmH from T. thermophilus abolished its IFN-α inducing potential. More importantly, Gm18-modified tRNA acted as TLR7 antagonist and blocked IFN-α induction of influenza A virus–infected PBMCs.

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