Epigenetic control of microglia polarization in brain pathologies

• Autorzy: Kaminska B.
• Języki publikacji: EN

Abstrakty

EN

Microglia are the myeloid cells residing in the central nervous system, quickly responding to pathological alterations. Microglia polarization refers to establishment of a specific phenotype which can produce detrimental or beneficial effects. The inflammatory (M1) and alternative, anti-inflammatory (M2) phenotype are the extreme phenotypes. It is poorly understood how microglia are reprogrammed in a responses to challenges and how signals are converted into sustained patterns of gene expression in brain pathologies. Transcriptome analysis of microglial cultures exposed to glioma (GCM) or lipopolysaccharide (LPS) shows activation of distinct signaling and metabolic pathways resulting in different patterns of gene expression. Studies of activating and repressive histone marksrevealed the early decrease of histone acetylation in microglia exposed to GCM, while changes in repressive histone modifications after GCM or LPS were delayed and correlated to transcription down-regulation. HDAC inhibitors blocked morphological changes associated with GCM or LPS treatment and reduced GCMinduced gene expression. Those results demonstrate that the inflammatory genes are epigenetically “primed” and easy to be induced in microglia, while the erasure of histone acetylation marksis prerequisite to put the repressive marks on M1 inflammatory genes and induce activating histone acetylation at the M2 genes. Studies of epigenetic patternsin sorted microglia were extended to a cerebral ischemia (MCAo) model, in which microglia activation is associated with the prolonged inflammation and subsequent neurodegeneration. Our results demonstrate that microglial polarization is mediated by alterations in gene expression and changes in their epigenetic patterns. Epigenetic modifications provide an additional step for the control of long-lasting changes in transcriptional programs in stimulated microglia.

• Wydawca: -
• Czasopismo: Acta Neurobiologiae Experimentalis
• Rocznik: 2015
• Tom: 75
• Numer: Supl.
• Opis fizyczny: p.S18

Twórcy

autor

Kaminska B.

• Laboratory of Molecular Neurobiology, Nencki Institute of Experimental Biology, Polish Academy of Sciences, Warsaw, Poland