Macrophage colony stimulating factor (CSF1) is a cytokine that is upregulated in 
several diseases of the central nervous system (CNS). To examine the effects of 
CSF1 overexpression on microglia, transgenic mice that overexpress CSF1 in the 
glial fibrillary acidic protein (GFAP) compartment were generated. CSF1 
overexpressing mice have increased microglial proliferation and increased 
microglial numbers compared with controls. Treatment with PLX3397, a small 
molecule inhibitor of the CSF1 receptor CSF1R and related kinases, decreases 
microglial numbers by promoting microglial apoptosis in both CSF1 overexpressing 
and control mice. Microglia in CSF1 overexpressing mice exhibit gene expression 
profiles indicating that they are not basally M1 or M2 polarized, but they do 
have defects in inducing expression of certain genes in response to the 
inflammatory stimulus lipopolysaccharide. These results indicate that the CSF1 
overexpression observed in CNS pathologies likely has pleiotropic influences on 
microglia. Furthermore, small molecule inhibition of CSF1R has the potential to 
reverse CSF1-driven microglial accumulation that is frequently observed in CNS 
pathologies, but can also promote apoptosis of normal microglia.