The Effect of Chronic Mild Stress and Venlafaxine on the Expression and Methylation Levels of Genes Involved in the Tryptophan Catabolites Pathway in the Blood and Brain Structures of Rats

Abstract

A growing body of evidence suggests that depression may be associated with impairment of the tryptophan catabolites (TRYCATs) pathway. The present study investigated the effects of the chronic administration of venlafaxine on the expression and methylation status of Katl, Tph1/2, Ido1, Kmo and Kynu in the brain and blood of rats exposed to the CMS model of depression. The rats were subjected to the CMS procedure for 2 or 7 weeks and administered venlafaxine (10 mg/kg/day, IP) for 5 weeks. mRNA and protein expression and the methylation status of gene promoters in PBMCs and six brain structures were evaluated and analysed using the TaqMan Gene Expression Assay and Western blotting, and methylation-sensitive high-resolution melting (MS-HRM), respectively. We found that the CMS procedure increased KatI expression in the midbrain and KatII expression in the midbrain and the amygdala, while venlafaxine administration decreased KatII expression in the hypothalamus and the cerebral cortex. The methylation status of the Tph1 and Kmo promoters in peripheral blood mononuclear cells (PBMCs) was significantly increased in the stressed group after antidepressant therapy. The protein levels of Tph1 and Ido1 were decreased following venlafaxine administration. Our results confirmed that CMS and venlafaxine modulate the expression levels and methylation status of genes involved in the TRYCATs pathway.

Dietary Habit Is Associated with Depression and Intelligence: An Observational and Genome-Wide Environmental Interaction Analysis in the UK Biobank Cohort

“…The regulation of the ephrin-Eph-c-Abl axis by PTPRJ plays a vital role in the proper central projection of retinal axons during development [ 53 ]. Wigner et al confirmed that venlafaxine modulated the expression and methylation level of KYNU in brain when rats were exposed to the chronic mild stress model of depression [ 54 ]. The SNP-dietary interactions suggest that PTPRJ and KYNU may play a role in alcohol-induced depression.…”

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

“…As well as changes in sensitivity to reward, the application of CMS and escitalopram therapy resulted in changes in the expression and methylation status of promoter regions of genes involved in oxidative and nitrosative stress, as well as the TRYCATs pathway. Similarly, previous animal studies suggest that such disorders may contribute to the development of depression [40][41][42][43]. In addition, patients with depression also demonstrate exacerbation of the oxidative process and insufficient antioxidant response, as well as overproduction of neurotoxic tryptophan metabolites such as quinolinic acid and 3-hydroxykynurenine [44,45].…”

Genome-wide environmental interaction analysis identifies dietary habit related risk loci for depression and intelligence in UK Biobank

“…The regulation of the ephrin-Eph-c-Abl axis by PTPRJ plays a vital role in the proper central projection of retinal axons during development [49]. Wigner et al con rmed that venlafaxine modulated the expression and methylation level of KYNU in brain when rats exposed to the chronic mild stress model of depression [50]. The SNP-dietary interactions suggest that PTPRJ and KYNU may play a role in alcohol-induced depression.…”