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.
Gowing
Genevieve
G
Centre de Recherche du Centre Hospitalier Universitaire de Québec, Department of Psychiatry and Neuroscience of Laval University, Quebec, Pavillon CHUL, 2705 Boulevard Laurier, Quebec, Canada.
Lalancette-Hébert
Mélanie
M
Audet
Jean-Nicolas
JN
Dequen
Florence
F
Julien
Jean-Pierre
JP
D000690:Amyotrophic Lateral Sclerosis / Q000139:chemically induced* / Q000473:pathology; D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D015214:Antigens, Differentiation, Myelomonocytic / Q000378:metabolism; D007150:Immunohistochemistry; D053583:Interleukin-1beta / Q000378:metabolism; D016173:Macrophage Colony-Stimulating Factor / Q000494:pharmacology*; D051379:Mice; D008822:Mice, Transgenic; D017628:Microglia / Q000187:drug effects*; D009154:Mutation / Q000502:physiology; D010525:Peripheral Nerves / Q000473:pathology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013116:Spinal Cord / Q000473:pathology; D013482:Superoxide Dismutase / Q000096:biosynthesis* / Q000235:genetics*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D000097382:CD68 Molecule
D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D053583:Interleukin-1beta; D016173:Macrophage Colony-Stimulating Factor; D013482:Superoxide Dismutase; D014409:Tumor Necrosis Factor-alpha; C081026:CD68 protein, mouse; D000097382:CD68 Molecule