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Updated: Jun 20, 2026
Depletion and Reconstitution of Macrophages in Mice
Published on: August 1, 2012
Macrophage colony stimulating factor (M-CSF) exacerbates ALS disease in a mouse model through altered responses of
Genevieve Gowing1, Mélanie Lalancette-Hébert, Jean-Nicolas Audet
1Centre de Recherche du Centre Hospitalier Universitaire de Québec, Department of Psychiatry and Neuroscience of Laval University, Quebec, Pavillon CHUL, 2705 Boulevard Laurier, Quebec, Canada.
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.
Insights
Macrophage colony stimulating factor (M-CSF) unexpectedly accelerated ALS progression in a mouse model. M-CSF treatment led to reduced motor neuron survival and increased inflammation, contrary to neuroprotective expectations.
Area of Science:
- Neuroscience
- Immunology
- Cell Biology
Background:
- Macrophage colony stimulating factor (M-CSF) is a cytokine crucial for microglial cell survival, proliferation, and maturation.
- M-CSF administration has shown potential for promoting neuronal survival in central nervous system (CNS) injury models.
Purpose of the Study:
- To investigate the neuroprotective potential of M-CSF in a mouse model of Amyotrophic Lateral Sclerosis (ALS).
- To determine if M-CSF could induce a neuroprotective microglial phenotype and enhance motor neuron survival in SOD1(G37R) mice.
Main Methods:
- Mutant SOD1(G37R) transgenic mice, modeling ALS, were weekly treated with M-CSF starting at disease onset.
- Evaluated disease progression, survival rates, muscle innervation, and microglial cell phenotype, including cytokine and marker expression.
Main Results:
- M-CSF treatment unexpectedly accelerated disease progression and shortened survival in SOD1(G37R) mice.
- Accelerated progression was linked to diminished muscle innervation and a shift in microglial cells towards a pro-inflammatory, macrophage-like phenotype.
- Upregulation of pro-inflammatory cytokines (TNF-alpha, IL-1 beta) and the phagocytic marker CD68 was observed in M-CSF-treated microglial cells.
Conclusions:
- M-CSF does not confer neuroprotection in the SOD1(G37R) ALS mouse model and instead exacerbates disease.
- The pro-inflammatory and phagocytic activation of microglial cells by M-CSF contributes to motor neuron degeneration and reduced survival in this ALS model.
