Microglial repopulation rewires and rejuvenates the aged brain

Changes in microglial form and function contribute to age-related cognitive impairment. Developing methods to target microglia is critical to understand and prevent the adverse effects of aging. Using a specific colony-stimulating factor 1 receptor (CSF1R) inhibitor, our lab has shown that the majority of microglia can be eliminated from the CNS (Elmore et al., 2014). Withdrawal of the CSF1R inhibitor, stimulates brain-wide repopulation with new cells, that express microglial markers (Elmore et al., 2014; Elmore et al., 2015). The impact of these newly repopulated cells on the aged brain has not been explored, but will provide useful insight into the role of microglia in aging. In addition, the therapeutic potential of replacing “primed” or “senescent” microglia in the aged brain with new cells is of great interest. Therefore, our goal was to fully characterize the gene expression profiles of the aged control vs. aged repopulated brains in comparison to young controls. mRNA from C57BL/6 male mouse whole-brain homogenates were analyzed. A total of 9 samples, including three from young control (~5 months of age at sacrifice), three from aged control (~24 months of age at sacrifice), and three from aged repopulated (microglia were eliminated for 2 weeks using a CSF1R inhibitor, then the inhibitor was removed, and new microglia were allowed to repopulate the entire brain for 4 weeks prior to sacrifice, ~24 months of age at sacrifice) mice.