Glial reactivity in response to neurotoxins: Relevance and methods

Abstract

Microglia and astrocytes become activated in response to diverse toxic exposures, regardless of the cellular or molecular targets affected; biomarkers of these responses, therefore, can be used to detect and localize damage to any area of the CNS. A variety of cellular and molecular markers of reactive microglia and astrocytes have been implemented to reveal all types of neural injuries, including those caused by chemical insults of the CNS. Recent advances in approaches to evaluate the cell-specific transcriptome in the CNS allow for an expansion of the existing repertoire of glial activation biomarkers. Here, we show how the approach we used to validate assays of glial fibrillary acidic protein (GFAP) as a biomarker of astrogliosis can be extended to a cell signaling-based assay via phosphorylation of signal transducer and activator of transcription 3 (STAT3). We also introduce new methods to assess cell type-specific gene expression, glial-specific pharmacological inhibition, and genetic manipulation that can be used to evaluate glial reactivity, with the overall goal of defining the microglial and astroglial activation phenotype that results from exposures to broad classes of neurotoxicants.