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Updated: Jun 19, 2025
Characterization and Isolation of Mouse Primary Microglia by Density Gradient Centrifugation
Published on: February 16, 2018
Mitochondrial respiration in microglia is essential for response to demyelinating injury but not proliferation
Joshua S Stoolman1, Rogan A Grant2, Taylor A Poor2
1Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL, USA. joshua.stoolman@northwestern.edu.
Abstract:
Microglia are necessary for central nervous system (CNS) function during development and play roles in ageing, Alzheimer's disease and the response to demyelinating injury1-5. The mitochondrial respiratory chain (RC) is necessary for conventional T cell proliferation6 and macrophage-dependent immune responses7-10. However, whether mitochondrial RC is essential for microglia proliferation or function is not known. We conditionally deleted the mitochondrial complex III subunit Uqcrfs1 (Rieske iron-sulfur polypeptide 1) in the microglia of adult mice to assess the requirement of microglial RC for survival, proliferation and adult CNS function in vivo. Notably, mitochondrial RC function was not required for survival or proliferation of microglia in vivo. RNA sequencing analysis showed that loss of RC function in microglia caused changes in gene expression distinct from aged or disease-associated microglia. Microglia-specific loss of mitochondrial RC function is not sufficient to induce cognitive decline. Amyloid-β plaque coverage decreased and microglial interaction with amyloid-β plaques increased in the hippocampus of 5xFAD mice with mitochondrial RC-deficient microglia. Microglia-specific loss of mitochondrial RC function did impair remyelination following an acute, reversible demyelinating event. Thus, mitochondrial respiration in microglia is dispensable for proliferation but is essential to maintain a proper response to CNS demyelinating injury.
Insights
Mitochondrial respiration is not essential for microglia survival or proliferation. However, impaired mitochondrial function in microglia hinders the central nervous system's ability to repair demyelinating injuries.
Area of Science:
- Neuroscience
- Immunology
- Cell Biology
Background:
- Microglia are crucial for central nervous system (CNS) development, function, and disease.
- Mitochondrial respiratory chain (RC) is vital for immune cell proliferation and function.
- The role of mitochondrial RC in microglia function remains unclear.
Purpose of the Study:
- To investigate the necessity of microglial mitochondrial RC for survival, proliferation, and CNS function.
- To assess the impact of impaired microglial mitochondrial RC on cognitive decline and demyelinating injury response.
Main Methods:
- Conditional deletion of the mitochondrial complex III subunit Uqcrfs1 in adult mouse microglia.
- RNA sequencing to analyze gene expression changes in microglia lacking RC function.
- Assessment of cognitive function, amyloid-β plaque interaction, and remyelination in vivo.
Main Results:
- Microglial mitochondrial RC function is dispensable for microglia survival and proliferation in vivo.
- Loss of RC function induced distinct gene expression changes in microglia, not typical of aging or disease.
- Microglia-specific RC deficiency did not cause cognitive decline or increase amyloid-β plaque load.
- Impaired microglial mitochondrial RC significantly hindered remyelination after demyelinating injury.
Conclusions:
- Microglial mitochondrial respiration is not required for microglia proliferation.
- Mitochondrial respiration in microglia is essential for an effective response to CNS demyelinating injury.
- Targeting microglial mitochondrial function may be a therapeutic strategy for CNS repair.
