Acute lung injury leads to depression-like symptoms through upregulation of neutrophilic and neuronal NADPH oxidase signaling in a murine model

Abstract

There is an increased prevalence of comorbid major depressive disorders with a number of inflammatory conditions which is thought to result from activation of the immune system. Acute lung injury (ALI) in humans has been also shown to be associated with depression previously. However, no study has explored the mechanism behind ALI-induced depression. NADPH oxidase (NOX-2) derived reactive oxygen species (ROS) are associated with neuropsychiatric disorders including depression. ROS generation via NOX-2 is also shown to be involved in the pathogenesis of ALI. Therefore, we hypothesized that ROS generation may be a common link between ALI and depression. The present study utilized LPS model of ALI in mice to explore the effect of lung inflammation on depression-like behavior and further delineate the role of NOX-2 signaling in it. ALI led to enhanced NOX-2 activation in neutrophils/brain and neuronal oxidative stress which was concurrent with depression-like symptoms as assessed by sucrose preference and tail suspension test. Role of neutrophilic NOX-2 in ALI-induced depression was confirmed by depletion of neutrophils as well NOX-2 inhibitor, apocynin. Both of these approaches led to reduction in depressive symptoms induced by ALI. The present study suggests that ALI-induced upregulation of neutrophilic NOX-2/ROS may contribute to depression-like symptoms in mice.

Keywords: Acute lung injury; Depression; NADPH oxidase; Neutrophils; ROS.