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

Authors
Journal
Experimental Neurology
0014-4886
Publisher
Elsevier
Publication Date
Volume
220
Issue
2
Identifiers
DOI: 10.1016/j.expneurol.2009.08.021
Keywords
  • Motor Neuron Disease
  • Amyotrophic Lateral Sclerosis
  • Macrophage-Colony Stimulating Factor (M-Csf)
  • Microglia
  • Macrophage
  • Neuroinflammation
  • Superoxide Dismutase 1 (Sod1)
  • Transgenic Mice
Disciplines
  • Medicine

Abstract

Abstract 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-α and IL-1β and of the phagocytic marker CD68.

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