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

Publication Type:

Journal Article

Authors:

Gowing, Geneviève; Lalancette-Hébert, Mélanie; Audet, Jean-Nicolas; Dequen, Florence; J-P Julien

Source:

Exp Neurol, Volume 220, Issue 2, p.267-75 (2009)

Keywords:

Amyotrophic Lateral Sclerosis, Animals, Antigens, CD, Antigens, Differentiation, Myelomonocytic, Immunohistochemistry, Interleukin-1beta, Macrophage Colony-Stimulating Factor, Mice, Mice, Transgenic, Microglia, Mutation, Peripheral Nerves, Reverse Transcriptase Polymerase Chain Reaction, Spinal Cord, Superoxide Dismutase, Tumor Necrosis Factor-alpha

Abstract:

<p>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.</p>