Since the role of white matter degenerating microglia in myelination failure is unclear, we sought to define the core features of this novel population of aging human microglia.
Researchers analyzed post-mortem human brain tissue to define a population of degenerative microglia (DM) in aging white matter lesions. They employed immunofluorescence staining and gene expression analysis to investigate molecular mechanisms related to the degeneration of DM.
Researchers found that DM accumulated myelin debris, were selectively enriched in the iron-binding protein light chain ferritin, and accumulated PLIN2-labeled lipid droplets. DM displayed lipid peroxidation injury and enhanced expression for TOM20, a mitochondrial translocase, and a sensor of oxidative stress. DM also displayed enhanced expression of the DNA fragmentation marker phospho-histone H2A.X. They identified a unique set of ferroptosis-related genes involving iron-mediated lipid dysmetabolism and oxidative stress that were preferentially expressed in white matter injury relative to gray matter neurodegeneration.
