Pubertal immune challenge blocks the ability of estradiol to enhance performance on cognitive tasks in adult female mice

SummaryPuberty is a period characterized by brain reorganization that contributes to the development of neural and behavioral responses to gonadal steroids. Previously, we have shown that a single injection of the bacterial endotoxin, lipopolysaccharide (LPS; 1.5 mg/kg IP), during the pubertal period (around 6 weeks old) in mice decreases sexual receptivity in response to estradiol and progesterone in adulthood. These findings suggest that pubertal immune challenge has an enduring effect of decreasing the behavioral responsiveness to gonadal steroid hormones. Since estradiol improves cognitive function in certain tasks in mice, we investigated the effect of pubertal immune challenge on the ability of estradiol to enhance cognitive function. We hypothesized that estradiol would be less effective at enhancing performance on particular cognitive tasks in female mice treated with LPS during puberty. Six-week old (pubertal) and 10-week old (adult) female CD1 mice were injected with either saline or LPS. Five weeks later, they were ovariectomized and implanted subcutaneously with either an estradiol- or oil-filled Silastic© capsule followed 1 week later with testing for cognitive function. The duration of juvenile investigation during social discrimination and recognition tests was used as a measure of social memory, and the duration of object investigation during object recognition and placement tests was used as a measure of object memory. Chronic estradiol treatment enhanced social and object memory in saline-treated females and in females treated with LPS in adulthood. In contrast, in females treated with LPS at 6 weeks old, estradiol failed to improve social and object memories. These results support the hypothesis that exposure to an immune challenge during puberty reduces at least some of the cognitive effects of estradiol. Moreover, these results support the idea that pubertal immune challenge compromises a wide variety of behavioral influences of ovarian hormones.