Microglial Homeostasis Requires Balanced CSF-1/CSF-2 Receptor Signaling
Violeta Chiţu, Fabrizio Biundo, Gabriel G. L. Shlager, Eun Su Park, Ping Wang, Maria Gulinello, Şölen Gökhan, Harmony C. Ketchum, Kusumika Saha, Michael DeTure, Dennis W. Dickson, Z. Wszolek, Deyou Zheng, Andrew L. Croxford, Burkhard Becher, Daqian Sun, Mark F. Mehler, E. Richard Stanley
Abstract
mice by preventing microgliosis and eliminating most microglial transcriptomic alterations, including those indicative of oxidative stress and demyelination. We also show elevation of Csf2 transcripts and of several CSF-2 downstream targets in the brains of ALSP patients, demonstrating that the mechanisms identified in the mouse model are functional in humans. Our data provide insights into the mechanisms underlying ALSP. Because increased CSF2 levels and decreased microglial Csf1r expression have also been reported in Alzheimer's disease and multiple sclerosis, we suggest that the unbalanced CSF-1R/CSF-2 signaling we describe in the present study may contribute to the pathogenesis of other neurodegenerative conditions.