Abstract # 3178 Maternal viral infection causes global changes in fetal microglia and alters gene expression and microglia density in the fetal amygdala

Abstract

Prenatal exposure to maternal infection increases the risk of neurodevelopmental disorders, though the mechanisms remain to be elucidated. We have previously established a maternal immune activation (MIA) swine model, which results in altered piglet social behaviors postnatally, without microglia activation. Here, we sought to identify microglia activity prenatally, immediately following maternal infection with live porcine reproductive and respiratory syndrome virus (PRRSV). Cesarean sections performed 7 and 21 days post-inoculation (dpi) revealed that MIA fetuses had reduced brain weights and that MIA microglia expressed more of the classical activation marker MHCII and reduced phagocytic and chemotactic activity compared to controls. High-throughput gene expression analysis of microglial-enriched genes revealed differential regulation in primary microglia and in whole amygdala tissue across both time points. Microglia density was increased in the fetal amygdala at 7 but not 21 dpi, though few changes in microglia number and morphology were evident in the fetal hippocampus. Our preliminary data also reveal sexual dimorphisms in gene expression patterns and microglia number and morphology across all time points and tissues, indicating that MIA likely induces dissimilar effects between males and females prenatally. Overall, these data suggest that fetal microglia, particularly in the amygdala, are transiently but significantly altered by maternal viral infection, indicating a potential mechanism through which MIA could negatively impact prenatal neurodevelopment and cause altered behaviors postnatally. Supported by NIH HD069899.