Interaction Between Gestational Immune Activation and Environmental Enrichment During Pregnancy on ER-α and Iba-1 Counts in the Postpartum Rat Hippocampus

Abstract

The maternal brain experiences a high level of plasticity during pregnancy which is understood to be largely mediated by changes to the maternal immune, endocrine and nervous systems to prepare for offspring care. Given the prevalence of infections during pregnancy, the effect of gestational immune activation (GIA) on these systems and the maternal brain have not been fully characterized. In this work, GIA is used with respect to immune activation in the dams, instead of the maternal immune activation (MIA) terminology that is typically used for offspring exposure. In addition to this, the protective effects of environmental enrichment against biological stressors such as an infection have only been investigated within the context of MIA offspring. This study examines the effects of lipopolysaccharide (LPS) induced GIA and housing conditions on the postpartum maternal hippocampus, a region of the brain that plays an in-direct role in supporting maternal behaviours. This is achieved through examining the number of ER-α positive cells and active microglia (Iba-1 positive cells) in the different layers of the postpartum maternal rat hippocampus. Nulliparous female Sprague-Dawley rats, housed in either animal care control (ACC) or environmental enrichment (EE) conditions, were treated with intraperitoneal injections of 100μg/kg lipopolysaccharides (LPS) or a pyrogen-free saline solution (VEH). Mothers were sacrificed on postpartum day 22 and brains were collected. Brains were preserved and later prepared for immunohistochemical labelling of ER-α and Iba-1 positive cells in the layers of the hippocampus (CA1, CA3 and Dentate Gyrus (DG): GrDG, MoDG, and PoDG). This project found a statistically significant effect of LPS treatment on the number of ER-α positive cells in the CA3 and in the PoDG layers of the hippocampus; LPS served to reduce the overall number of estrogen receptors in these areas. These findings support the potential for immune challenges to disrupt the adaptations made to maternal neuroendocrine pathways that prepare for post-pregnancy offspring care.