Macrophage colony stimulating factor (M-CSF) exacerbates ALS disease in a mouse model through altered responses of microglia expressing mutant superoxide dismutase

Macrophage colony stimulating factor (M-CSF) is a cytokine that regulates the Survival, proliferation and maturation of microglial cells. Administration of M-CSF can promote neuronal survival in various models of central nervous system (CNS) injury. Here, in an attempt to induce a neuroprotective microglial cell phenotype and enhance motor neuron survival, mutant SOD1(G37R) transgenic mice were treated, weekly, with M-CSF starting at onset of disease. Unexpectedly, M-CSF accelerated disease progression in SOD1(G37R) mouse model of ALS. The shortened survival of M-CSF-treated animals was associated with diminished muscle innervation and enhanced adoption of a macrophage-like phenotype by microglial cells characterised by the upregulation of pro-inflammatory cytokines TNF-alpha and IL-1 beta and of the phagocytic marker CD68. (C) 2009 Elsevier Inc. All rights reserved.