Microglia Regulate Cell Genesis in a Sex-dependent Manner in the Neonatal Hippocampus

Abstract

Microglia, the innate immune cells of the brain, regulate brain development through many processes such as synaptic pruning, supporting cell genesis and phagocytosing living and dying cells. There are sex differences in these same developmental processes throughout the brain, thus microglia may contribute to brain sex differences. We examined whether microglia support a known sex difference in neonatal hippocampal neurogenesis and whether juvenile hippocampal neurogenesis was impacted by the loss of neonatal microglia. We used central infusion of liposomal clodronate to selectively deplete microglia and found decreased cell genesis in the male, but not female, dentate gyrus and hippocampus. We found that loss of microglia decreased cell genesis in the cortex and amygdala of both males and females. We assessed the expression of several cytokines and growth factors that have previously been shown to support cell genesis. We found that expression of Il1b and Tnf were decreased in the hippocampus due to microglia depletion however, there were no sex differences in the expression of any immune genes. In adolescence, there was an increase in the number of mitotic cells in the subgranular zone of the dentate gyrus of previously microglia depleted rats however, the number of newly-born neurons was unchanged in the adolescent animals. We also sought to determine whether there was a sex difference in the number of progenitor cells in the dentate gyrus in the neonatal period. We found no sex differences in the number of progenitor cells. Overall, these studies show that microglia are important for regulating region-specific sex differences in cell genesis in the developing brain.