Aging-like changes in the transcriptome of irradiated microglia

Matthew D. Li, Terry C. Burns, Sunny Kumar, Alexander A. Morgan, Steven A. Sloan, Theo D. Palmer

Research output: Contribution to journalArticlepeer-review

27 Scopus citations


Whole brain irradiation remains important in the management of brain tumors. Although necessary for improving survival outcomes, cranial irradiation also results in cognitive decline in long-term survivors. A chronic inflammatory state characterized by microglial activation has been implicated in radiation-induced brain injury. We here provide the first comprehensive transcriptional profile of irradiated microglia. Fluorescence-activated cell sorting was used to isolate CD11b+ microglia from the hippocampi of C57BL/6 and Balb/c mice 1 month after 10 Gy cranial irradiation. Affymetrix gene expression profiles were evaluated using linear modeling and rank product analyses. One month after irradiation, a conserved irradiation signature across strains was identified, comprising 448 and 85 differentially up- and downregulated genes, respectively. Gene set enrichment analysis demonstrated enrichment for inflammation, including M1 macrophage-associated genes, but also an unexpected enrichment for extracellular matrix and blood coagulation-related gene sets, in contrast previously described microglial states. Weighted gene coexpression network analysis confirmed these findings and further revealed alterations in mitochondrial function. The RNA-seq transcriptome of microglia 24-h postradiation proved similar to the 1-month transcriptome, but additionally featured alterations in apoptotic and lysosomal gene expression. Reanalysis of published aging mouse microglia transcriptome data demonstrated striking similarity to the 1-month irradiated microglia transcriptome, suggesting that shared mechanisms may underlie aging and chronic irradiation-induced cognitive decline.

Original languageEnglish (US)
Pages (from-to)754-767
Number of pages14
Issue number5
StatePublished - May 1 2015


  • Aging
  • Brain radiation
  • Extracellular matrix
  • Hippocampus
  • Inflammation

ASJC Scopus subject areas

  • Neurology
  • Cellular and Molecular Neuroscience


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