Colony Stimulating Factor-1 (CSF-1) and Interleukin-34 (IL-34) Differentially Alter White Matter and Gray Matter Microglia and Oligodendrocyte Progenitor Cells

Abstract

Colony stimulating factor-1 receptor (CSF-1R) signaling is necessary for microglia development and maintenance throughout life. The CSF-1R ligands, CSF-1 and interleukin-34 (IL-34), are indispensable for microglia survival in white matter and gray matter, respectively. While CSF-1 has been studied to a greater extent, the role of IL-34 in microglia function and in the brain overall is much less understood. Here, we examined the region-specific effects of intracerebroventricular (i.c.v.) CSF-1 and IL-34 administration on microglia and oligodendrocyte lineage cells in mice at two timepoints. At 3 days post-intervention, IL-34 increased microglial CD68 levels and the microglia population in the hippocampal CA1 region, whereas CSF-1 increased the microglia population in the corpus callosum. Furthermore, CSF-1, but not IL-34, reduced the oligodendrocyte progenitor cell population in the corpus callosum. These effects were no longer observed at 7 days, revealing the transient nature of the microglial response. Together, these findings demonstrate that in addition to relying on specific signals for survival, microglia respond differently to CSF-1R ligands in a brain microenvironment-dependent manner. These findings highlight the need to better understand microglia in the context of their location, which could provide key insights into the pathogenesis of neuroimmune disorders that predominantly affect gray matter or white matter areas.