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Updated: Dec 5, 2025
Isolation of Cortical Microglia with Preserved Immunophenotype and Functionality From Murine Neonates
Published on: January 30, 2014
Modifying macrophages at the periphery has the capacity to change microglial reactivity and to extend ALS survival
Aude Chiot1, Sakina Zaïdi1, Charlène Iltis1
1Sorbonne Université, Institut du Cerveau - Paris Brain Institute - ICM, Inserm, CNRS, Paris, France.
Abstract:
Microglia and peripheral macrophages have both been implicated in amyotrophic lateral sclerosis (ALS), although their respective roles have yet to be determined. We now show that macrophages along peripheral motor neuron axons in mouse models and patients with ALS react to neurodegeneration. In ALS mice, peripheral myeloid cell infiltration into the spinal cord was limited and depended on disease duration. Targeted gene modulation of the reactive oxygen species pathway in peripheral myeloid cells of ALS mice, using cell replacement, reduced both peripheral macrophage and microglial activation, delayed symptoms and increased survival. Transcriptomics revealed that sciatic nerve macrophages and microglia reacted differently to neurodegeneration, with abrupt temporal changes in macrophages and progressive, unidirectional activation in microglia. Modifying peripheral macrophages suppressed proinflammatory microglial responses, with a shift toward neuronal support. Thus, modifying macrophages at the periphery has the capacity to influence disease progression and may be of therapeutic value for ALS.
Insights
Peripheral macrophages and microglia play roles in amyotrophic lateral sclerosis (ALS). Modulating peripheral macrophages in ALS mice reduced inflammation, delayed disease, and improved survival, suggesting therapeutic potential.
Area of Science:
- Neuroimmunology
- Neurodegenerative Diseases
- Cellular Biology
Background:
- Microglia and peripheral macrophages are implicated in amyotrophic lateral sclerosis (ALS).
- Their distinct roles in ALS pathogenesis remain unclear.
- Macrophages are observed along peripheral motor neuron axons in ALS models and patients.
Purpose of the Study:
- To investigate the roles of microglia and peripheral macrophages in ALS.
- To determine the impact of modulating peripheral myeloid cells on ALS progression.
- To elucidate the differential responses of macrophages and microglia to neurodegeneration.
Main Methods:
- Analysis of macrophages along peripheral motor neuron axons in ALS mouse models and patients.
- Investigating peripheral myeloid cell infiltration into the spinal cord.
- Targeted gene modulation of the reactive oxygen species pathway in peripheral myeloid cells via cell replacement in ALS mice.
- Transcriptomic analysis of sciatic nerve macrophages and microglia.
Main Results:
- Peripheral myeloid cell infiltration into the spinal cord was limited and disease duration-dependent.
- Gene modulation in peripheral myeloid cells reduced both peripheral macrophage and microglial activation.
- This modulation delayed ALS symptoms and increased survival in mice.
- Sciatic nerve macrophages and microglia exhibited distinct temporal responses to neurodegeneration.
- Modifying peripheral macrophages suppressed proinflammatory microglial responses, promoting neuronal support.
Conclusions:
- Peripheral macrophages and microglia exhibit differential responses to neurodegeneration in ALS.
- Modulating peripheral macrophages can influence microglial activation and promote neuronal support.
- Targeting peripheral macrophages offers potential therapeutic strategies for ALS treatment.
