MICROGLIA INFLUENCE ASTROCYTE MATURATION IN THE DEVELOPING HIPPOCAMPUS

Microglia and astrocytes, along with oligodendrocytes, represent the major glial cell types in the brain. While microglia cells originate in the yolk sac during primitive hematopoiesis, astrocytes differentiate from neural stem cells later in brain development. Thus, microglia invasion preceding astrogenesis may support a role for microglia in promoting and guiding astrocyte maturation. However, very little is known about how microglia influence these cells in early brain development. Here, we set out to investigate the role of microglia in the process of astrocyte maturation during early postnatal development. We used an established model of microglial dysfunction, the Cx3cr1 knockout mouse line, in which microglia lack the fractalkine receptor,to study how defective microglia could affect astrocytes at different postnatal time points and in adulthood. We found that the density of glutamine synthetase (GS)-positive astrocytes during the second and third postnatal weeks was significantly increased in the hippocampal CA1 region of KO mice, suggesting that microglial dysfunction impact astrocytes. Using sparse astrocyte labeling and confocal microscopy, we conducted morphometric analyses and found that, during the same developmental window, astrocytes from KO mice occupied a larger volume and exhibited increased neuropil volume infiltration compared to controls. In adult mice, both astrocyte density and morphology were restored to control levels. Imaging of the astrocyte mitochondrial network showed that KO mice displayed reduced mitochondrial density during the second postnatal week. Further analyses are ongoing to assess the underlying mechanisms. Overall, our results suggest that microglia impact astrocyte density and morphology during early postnatal brain development.