The role of oxidative and nitrosative stress and the tryptophan catabolites pathway in the pathogenesis of depression

Abstract

Depression is the most common mental illness, affecting approximately 350 million people around the world. Despite numerous studies, the etiology of this disease remains unclear. Previous studies suggest the involvement of interrelated biochemical pathways, i.e. oxidative and nitrative stress as well as abnormalities of the tryptophan catabolites pathway (TRYCATs) in the depression development. Therefore, the aim of this study was to explain the role of oxidative and nitrative stress as well as disorders in the course of the TRYCATs pathway in the molecular basis of depression. In this study, an attempt was made to determine the effect of single nucleotide polymorphisms, located in genes, encoding enzymes involved in oxidative and nitrative stress, and the TRYCATs pathway on the incidence of depression. Moreover, using an in vivo model of depression, the impact of chronic mild stress stimuli on mRNA expression and protein amount as well as the degree of methylation of the promoter regions of genes encoding enzymes involved in the studied pathways was assessed. The obtained results clearly confirmed the studied biochemical pathways are involved in the development of depression at the molecular level.