Macrophage colony stimulating factor (M-CSF) exacerbates ALS disease in a mouse model through altered responses of microglia expressing mutant superoxide dismutase
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.
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Depending on the nature of the CNS insult, increased microglial phagocytosis may ameliorate or worsen pathology.
“Depending on the nature of the CNS insult, increased microglial phagocytosis may ameliorate 46 or worsen pathology.56”
From CX3CR1 Deficiency Alters Microglial Activation and Reduces Beta-Amyloid Deposition in Two Alzheimer's Disease Mouse Models (2010) · cites this paper as [56]
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References 93 · Cited by 53
- Authors
- Gowing, G., Lalancette-Hébert, M., Audet, J.-N., Dequen, F., & Julien, J.-P.
- Affiliations
- Centre hospitalier universitaire de Québec (CA)
- Corresponding author
- Julien, Jean-Pierre
- Venue
- Experimental Neurology
- Publisher
- Elsevier BV
- Published
- 2009-12
- Volume
- 220
- Issue
- 2
- Pages
- 267-275
- ISSN
- 0014-4886 (ISSN-L)
- OpenAlex
- W1964309806
- Cited by
- 53
- References
- 93
- Citations by year
- 2025: 1 · 2024: 1 · 2023: 1 · 2022: 1 · 2021: 4 · 2020: 3 · 2019: 3 · 2018: 1 · 2017: 5 · 2016: 6 · 2015: 4 · 2014: 5 · 2013: 4 · 2012: 5
- FWCI
- 2.98
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- Locations
- Experimental Neurology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Canadian Institutes of Health Research
- Topics
- Health Sciences › Medicine › Neurology › Amyotrophic Lateral Sclerosis Research
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Keywords
- macrophage colony-stimulating factor, amyotrophic lateral sclerosis, microglia, disease progression, inflammatory cytokines, TNF-α, IL-1β, CD68, muscle innervation, motor neuron survival, neuroinflammation
- MeSH terms
- CD68 Molecule, Amyotrophic Lateral Sclerosis, Animals, Immunohistochemistry, Mice, Transgenic, Mutation, Peripheral Nerves, Spinal Cord, Superoxide Dismutase, Tumor Necrosis Factor-alpha, Antigens, Differentiation, Myelomonocytic, Antigens, CD, Macrophage Colony-Stimulating Factor, Microglia, Reverse Transcriptase Polymerase Chain Reaction, Mice, Interleukin-1beta
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