Sexually dimorphic effects of lipopolysaccharide on spatial memory

Deficits in hippocampal-dependent memory tasks following lipopolysaccharide (LPS) administration are frequently reported. However, prior work has predominantly been conducted with males. Given recent reports showing sex-related differences in the cognitive effects of an acute LPS challenge, the present study evaluated whether sex differences in spatial learning and memory exist. Adult female and male C57BL/6 J mice were evaluated for spatial learning and memory in a hidden platform version of the water maze following administration of LPS (0.25 mg/kg) prior to the first day of training. Results showed that LPS impaired spatial memory in males but had no effect on memory in females. Females and males showed differential use of behavioral search strategies during the probe trial, which may contribute to the selective vulnerability seen in males. Assessment of hippocampal and splenic inflammatory markers showed similar LPS-induced expression across the sexes, indicating that cytokine induction does not produce comparable cognitive deficits in males and females. However, males showed higher hippocampal expression of the interleukin type 1 receptor accessory proteins (AcP and AcPb) relative to females that may alter the impact of inflammation on the hippocampus. Ultimately, these data extend recent findings of sex-dependent effects of LPS on cognition to the water maze and emphasize the importance of reporting and comparing subjects' biological sex.