Microglia Activity in the Mouse Brain Lacking Prostaglandin E2-Connection to Autism

Prostaglandin E2 (PGE2) is a signaling molecule produced by cyclooxygenase2 (COX-2) that is important for brain development and microglial activation. Abnormal COX2/PGE2 signaling has been linked to Autism Spectrum Disorders (ASD). We aim to determine the impact of abnormal signaling of the COX-2/PGE2 pathway on microglial density and morphology in the developing brain of COX-2-KI mice. Using immunohistochemistry, we show at embryonic day 19 (E19) and postnatal day 25 (P25) COX-2-KI mice had sex and regional specific differences in microglial density, activation state, branch length, and branching networks. We show for the first time that these trajectories were influenced not only by the COX-2 deficiency, but also by sex, brain region, and developmental stage. These novel findings provide additional evidence that abnormal COX-2/PGE2 signaling can result in a disruption of microglial density and morphology during development and contribute to brain pathologies that result in ASDs.