Role of Tyrosine Nitrosylation in Stress-Induced Major Depressive Disorder: Mechanisms and Implications

Major depressive disorder (MDD) has a lifetime prevalence of approximately 10% and is one the most common diseases worldwide. Although many pathogenetic mechanisms MDD have been proposed, molecular details unifying hypothesis pathogenesis remain to be defined. Here, we investigated whether tyrosine nitrosylation, which caused by reaction C-atom 3 phenol ring with peroxynitrate (ONOO−), plays role in experimental MDD, because nitrosylation may affect cell functions altered MDD. To this end, induced stress through glucocorticoid application or chronic environmental unpredictable determined hippocampus immuno-staining ELISA. The catalases peroxidases for was measured using enzyme assays. We show that glucocorticoid- hippocampus. Long-term treatment stressed mice classical antidepressants amitriptyline fluoxetine prevented nitrosylation. Tyrosine also i.v. anti-ceramide antibodies recombinant ceramidase neutralize degrade, respectively, blood plasma ceramide recently shown induce Finally, phosphatidic acid, previously reduced upon stress, reverted stress-induced inhibition interfering formation NO radicals at least partly restored normal behavior mice. These data suggest might contribute targeting process