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

Abstract

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.

Ongoing Use of SSRIs Does Not Alter Outcome in Hospitalized COVID-19 Patients: A Retrospective Analysis

“…The potential value of selective serotonin reuptake inhibitors (SSRIs) and selective norepinephrine reuptake inhibitors (SNRIs), typically prescribed for anxiety, depression and obsessive-compulsive disorder (OCD), has been discussed significantly in the scientific literature [ 8 ] and lay press [ 9 ]. Numerous in vitro studies have carefully delineated multiple inflammatory pathways in which SSRIs and SNRIs might be beneficial in reducing inflammation [ 10 , 11 , 12 , 13 , 14 ]. The key role of inflammation in the progression, morbidity, and mortality of COVID-19 has been well documented in the medical literature and cytokine storm syndrome is a life-threatening feature of severe COVID-19 [ 8 , 15 , 16 , 17 ].…”

Molecular, circuit, and stress response characterization of Ventral Pallidum Npas1-neurons

“…Interestingly, Smads (including Smad2) are the main signal transductors activated by the TGF-beta signaling (Hiew et al, 2021), which have being implicated in the effects of stress and depression. For example, TGF-beta mRNA expression is reduced in the amygdala of Wistar rats exposed to chronic mild stress (Bialek et al, 2021). Further, chronic treatment of clinically used antidepressants in rodents increases TGF-beta signaling in the frontal cortex and hippocampus (Dow, 2005; Trojan et al, 2017).…”

Systemic concentrations of IL-18, TFG-, RANTES, ICAM-1 and uPAR as combined pathway-related factors may help in identification of patients suffering from depressive disorder

“…A preclinical study by Białek et al . [ 24 ] confirmed an association between TGF-β gene expression and methylation in depressive disorder. The findings of the current study are that the serum ICAM-1 concentrations were significantly lower in controls than in patients.…”

“…Similar to our results, the study by Davami et al [23] presented higher concentration of TGFβ in depression compared to controls. A preclinical study by Białek et al [24] confirmed an association between TGF-β gene expression and methylation in depressive disorder. The findings of the current study are that the serum ICAM-1 concentrations were significantly lower in controls than in patients.…”

“…Regarding age, the median ages of the control and rDD groups were 48.5 (44-53) and 49 (46-52) years, respectively. The clinical data of patients are as follows: number of depressive episodes 2 (1-4); 1.5 (-3); number of hospitalizations 1 (1-2); duration of the disease in years 2 (1-6); HDRS (Hamilton Depression Rating Scale (HDRS)) at the beginning of hospitalization 24 (20)(21)(22)(23)(24)(25)(26)(27)(28).…”