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Updated: Jun 20, 2026
Isolation of Cortical Microglia with Preserved Immunophenotype and Functionality From Murine Neonates
Published on: January 30, 2014
Mutant SOD1 G93A microglia have an inflammatory phenotype and elevated production of MCP-1
Siranush A Sargsyan1, Daniel J Blackburn, Siân C Barber
1Department of Neuroscience, School of Medicine and Biomedical Sciences, The University of Sheffield, UK.
Abstract:
The inflammatory response in amyotrophic lateral sclerosis (ALS) is well documented but the underlying cellular mechanisms have not been fully elucidated. We report that microglia isolated from the mutant human superoxide dismutase 1 (SOD1) G93A transgenic mouse model of ALS have an increased response to the inflammatory stimulus, lipopolysaccharide. Cell surface area and F4/80 surface marker, both indicators of cell activation, are increased relative to transgenic wild-type human SOD1 microglia. Monocyte chemoattractant protein-1, known to be increased in ALS, is produced at three-fold higher levels by SOD1 G93A than by wild-type human SOD1 microglia, under activating conditions. This novel finding implicates ALS microglia as a source of the increased monocyte chemoattractant protein-1 levels detected in ALS patients and in the ALS mouse model.
Insights
Microglia from a mouse model of amyotrophic lateral sclerosis (ALS) show heightened inflammatory responses. These activated microglia, specifically from the SOD1 G93A model, produce significantly more monocyte chemoattractant protein-1, implicating them in ALS pathogenesis.
Area of Science:
- Neuroimmunology
- Cellular mechanisms of neurodegeneration
Background:
- The inflammatory response is a known factor in amyotrophic lateral sclerosis (ALS).
- The specific cellular contributors and mechanisms driving this inflammation in ALS remain incompletely understood.
Purpose of the Study:
- To investigate the inflammatory response of microglia in the context of amyotrophic lateral sclerosis (ALS).
- To identify specific cellular changes and molecular mediators involved in microglial activation in an ALS mouse model.
Main Methods:
- Isolation of microglia from SOD1 G93A transgenic mice (ALS model) and wild-type littermate controls.
- Stimulation of microglia with lipopolysaccharide (LPS) to assess inflammatory response.
- Analysis of cell surface markers (F4/80) and cell surface area as indicators of activation.
- Quantification of monocyte chemoattractant protein-1 (MCP-1) production.
Main Results:
- Microglia from SOD1 G93A mice exhibited an amplified response to lipopolysaccharide compared to wild-type microglia.
- Increased cell surface area and F4/80 expression indicated heightened activation in SOD1 G93A microglia.
- SOD1 G93A microglia produced threefold higher levels of monocyte chemoattractant protein-1 (MCP-1) when activated.
Conclusions:
- ALS-associated microglia display an exaggerated inflammatory phenotype.
- These findings identify ALS microglia as a significant source of elevated MCP-1, a key chemokine implicated in ALS progression.
