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Updated: May 5, 2026
Three-dimensional Confocal Analysis of Microglia/macrophage Markers of Polarization in Experimental Brain Injury
Published on: September 4, 2013
Transcriptional Remodeling of Microglia After Experimental Myocardial Infarction
Jan Traub1,2, Nico Hofmann1,2, Clément Cochain3,4
1Department of Internal Medicine I, University Hospital Würzburg, 97080 Wuerzburg, Germany.
Abstract:
Beyond cardiac impairment, myocardial infarction (MI) affects the central nervous system (CNS), where it has been associated with neuroinflammation and cognitive dysfunction. Microglia, the resident immune cells of the CNS, are key regulators of neuroinflammatory processes. However, the transcriptional landscape of microglia following MI remains incompletely understood. We hypothesized that MI induces transcriptional remodeling in microglia that may reflect altered metabolic regulation. Male C57BL/6J mice underwent permanent LAD ligation or sham surgery. Five days post-MI, CD45-intermediate and SiglecH/CD11b-positive immune cells were isolated from cortical and subcortical regions by FACS and subjected to single-cell RNA sequencing. Complementary exploratory metabolic assays included assessment of mitochondrial mass and membrane potential as well as glucose uptake. Microglia represented the predominant immune cell population in both the cortex and subcortex. Subclustering revealed a significantly increased proportion of a "low translational" microglial subset after MI. Pseudobulk differential expression and gene set enrichment analyses demonstrated significant downregulation of translation-related pathways in cortical microglia and proteostasis-associated pathways in subcortical microglia. These transcriptional changes were accompanied by a significant reduction in mitochondrial mass and metabolic observations consistent with altered energetic regulation, although several functional readouts did not reach statistical significance. Experimental MI is associated with region-specific transcriptional remodeling of microglia, characterized by reduced expression of energy-intensive and proteostasis-related pathways. Exploratory metabolic observations are consistent with altered energetic regulation but require confirmation in adequately powered studies. These findings suggest that systemic cardiac injury is linked to microglial transcriptional adaptation in the early post-infarction phase.
Insights
Myocardial infarction (MI) alters brain immune cells called microglia. Following heart attack, microglia show reduced energy and protein regulation pathways, suggesting metabolic changes in the central nervous system (CNS).
Area of Science:
- Neuroscience
- Immunology
- Metabolism
Background:
- Myocardial infarction (MI) impacts the central nervous system (CNS), leading to neuroinflammation and cognitive issues.
- Microglia, the CNS's immune cells, regulate neuroinflammation, but their transcriptional changes post-MI are unclear.
- Altered microglial metabolism may underlie neuroinflammation following cardiac events.
Purpose of the Study:
- To investigate the transcriptional landscape of microglia in the CNS after experimental myocardial infarction (MI).
- To explore potential alterations in microglial metabolic regulation following MI.
- To understand the early transcriptional adaptations of microglia in response to systemic cardiac injury.
Main Methods:
- Permanent LAD ligation or sham surgery in male C57BL/6J mice.
- Isolation of immune cells (CD45-intermediate, SiglecH/CD11b-positive) from cortical and subcortical regions via FACS 5 days post-MI.
- Single-cell RNA sequencing, pseudobulk differential expression, and gene set enrichment analyses.
- Exploratory metabolic assays including mitochondrial mass, membrane potential, and glucose uptake.
Main Results:
- Microglia were the predominant immune cell type in both brain regions.
- A subset of microglia with reduced translational activity significantly increased post-MI.
- Downregulation of translation-related pathways in cortical microglia and proteostasis pathways in subcortical microglia was observed.
- Reduced mitochondrial mass and metabolic changes consistent with altered energetic regulation were noted, though not all functional readouts reached statistical significance.
Conclusions:
- Experimental MI induces region-specific transcriptional remodeling in microglia.
- Microglial adaptation involves reduced expression of energy-intensive and proteostasis-related pathways.
- Early metabolic observations suggest altered microglial energetic regulation post-MI, warranting further investigation.
