116. Sex differences in microglial morphology and number: Implications for function and behavior

Abstract

Males and females exhibit marked differences in prevalence and age of onset of neuropsychiatric disorders. Males are more likely to have disorders that arise early in life (e.g. autism), whereas females exhibit disorders arising around puberty (e.g. depression). No sex-based neurobiological differences have been described that can explain this sexual dimorphism. We show that male rats and mice have increased numbers of microglia in the hippocampus (HP) at postnatal day 4 (P4) than females. Neonatally-infected male rats also display cognitive deficits in adulthood when subjected to a systemic lipopolysaccharide (LPS) injection that induces an exaggerated IL-1β response within the HP of these rats. On the contrary, females are protected from this inflammatory response and cognitive deficit. Microglia play a critical role in synaptic pruning during neurodevelopment. Thus, increased numbers of microglia in neonatal male compared to female mice during critical stages of early synapse formation and maturation may adversely subject males to early-life infection by affecting synaptic pruning function of microglia. Insufficient or excess synaptic pruning due to inflammatory microglia may have enduring consequences on behavior and cognition in adulthood. Ongoing studies are aimed at determining the underlying mechanism behind heightened susceptibility of males by using Cx3cr1 -cre x MyD88 -flox mice, as well as investigating differences in synaptic pruning abilities of male vs. female microglia either in the presence or absence of immune challenge.