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Primary Cultures of Rat Astrocytes and Microglia and Their Use in the Study of Amyotrophic Lateral Sclerosis
Published on: June 23, 2022
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Chronically activated microglia in ALS gradually lose their immune functions and develop unconventional proteome
Romina Barreto-Núñez1, Louis-Charles Béland1, Hejer Boutej1
1CERVO Research Centre, Laval University, Quebec City, Quebec, Canada.
Glia
|April 5, 2024
Summary
Microglia in amyotrophic lateral sclerosis (ALS) lose immune function and develop unique protein profiles. These diseased cells become inefficient, shifting focus from immunity to RNA metabolism as ALS progresses.
Area of Science:
- Neuroscience
- Immunology
- Cell Biology
Background:
- Neuroinflammation and chronic microglial activation are hallmarks of amyotrophic lateral sclerosis (ALS).
- While mRNA changes in diseased microglia are known, their proteome is poorly understood.
Purpose of the Study:
- To functionally characterize and analyze the proteome of microglial cells at various disease stages in the SOD1-G93A mouse model of ALS.
- To investigate the molecular signatures and functional changes of microglia during ALS progression.
Main Methods:
- Functional assays on microglia from symptomatic SOD1-G93A mice.
- Proteomic analysis of microglial cells at early and advanced disease stages.
- Comparison with age-matched control microglia and human sporadic ALS spinal cord samples.
Main Results:
- Microglia exhibited a high mitotic index, reduced phagocytic capacity, and diminished immune responses.
- Distinct proteomic signatures emerged: immune proteins (GPNMB, HMBOX1) at early stages, and unconventional proteins (rootletin, vault proteins, STK38) at advanced stages.
- Upregulation of GPNMB and rootletin observed in human sporadic ALS spinal cords.
- Advanced-stage microglia showed functions enriched in RNA metabolism, not immunity.
Conclusions:
- Chronically activated microglia in ALS develop unconventional protein signatures.
- Microglia gradually lose immune identity and become functionally inefficient during ALS.
- These findings highlight a shift in microglial function away from immune roles towards RNA metabolism in advanced ALS.
