Abstract
NADPH oxidase is a source of reactive oxygen species (ROS) that have been implicated in the pathogenesis of various neurological disorders. We here demonstrated the involvement of a non-phagocytic type of NADPH oxidase, NOX1, in the hallmarks of major depressive disorders, including behavioral, biochemical and anatomical changes in mice. Oxidation of NMDA receptor 1 (NR1) by NOX1-derived ROS was depicted in the prefrontal cortex (PFC) , which could be causally linked to down-regulation of BDNF, promoting depressive-like behaviors. Given that NOX1 was up-regulated in the ventral tegmental area but not in PFC, mesocortical projections may play a crucial role in NOX1-dependent depressive-like behaviors. Our study present the potential molecular mechanism underlying the development of major depression through NOX1-induced oxidation of NR1 and epigenetic modification of the bdnf gene.
