The Sex-specific Effects of LPS on Depressive-like Behavior and Oxidative Stress in the Hippocampus of the Mouse

Abstract

Many human and animal studies have implicated inflammation as a mediator of oxidative stress and a possible contributor to hippocampal atrophy in the pathophysiology of major depressive disorder. We aimed to examine the effect of peripheral, systemic inflammation on oxidative stress and apoptosis in the hippocampi of male and female mice. We hypothesized that (1) lipopolysaccharide (LPS) would induce depressive-like behavior and hippocampal oxidative stress after 1 day in males, and (2) that a single LPS exposure would result in hippocampal apoptosis at 28 days. Further, we predicted that female sex would confer protection from the molecular and behavioral deleterious effects of LPS. Males exhibited depressive-like behavior 24 h after LPS administration compared to the males given saline. Female mice did not exhibit depressive-like behavior after LPS compared to females in the saline group. Males given LPS also had increased levels of superoxide dismutase (SOD) I in the hippocampus by 24 h compared to the saline group. At 28 days, we found decreased levels of brain derived neurotrophic factor (BDNF) protein in males given LPS compared to males given saline. Moreover, males given LPS showed increased apoptosis. Our work will provide insight into the underlying biology in males and females with MDD, and potentially underlying differences between the sexes. Also, our work will hopefully inform optimal clinical treatments that may indeed differ between the sexes.