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

Exp Neurol. 2009 Dec;220(2):267-75. doi: 10.1016/j.expneurol.2009.08.021. Epub 2009 Sep 3.

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-alpha and IL-1 beta and of the phagocytic marker CD68.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amyotrophic Lateral Sclerosis / chemically induced*
  • Amyotrophic Lateral Sclerosis / pathology
  • Animals
  • Antigens, CD / metabolism
  • Antigens, Differentiation, Myelomonocytic / metabolism
  • Immunohistochemistry
  • Interleukin-1beta / metabolism
  • Macrophage Colony-Stimulating Factor / pharmacology*
  • Mice
  • Mice, Transgenic
  • Microglia / drug effects*
  • Mutation / physiology
  • Peripheral Nerves / pathology
  • Reverse Transcriptase Polymerase Chain Reaction
  • Spinal Cord / pathology
  • Superoxide Dismutase / biosynthesis*
  • Superoxide Dismutase / genetics*
  • Tumor Necrosis Factor-alpha / metabolism

Substances

  • Antigens, CD
  • Antigens, Differentiation, Myelomonocytic
  • CD68 protein, mouse
  • Interleukin-1beta
  • Tumor Necrosis Factor-alpha
  • Macrophage Colony-Stimulating Factor
  • Superoxide Dismutase