Decoding the Transcriptional Response to Ischemic Stroke in Young and Aged Mouse Brain

Decoding the Transcriptional Response to Ischemic Stroke in Young and Aged Mouse Brain. Androvic P, Kirdajova D, Tureckova J, Zucha D, Rohlova E, Abaffy P, Kriska J, Valny M, Anderova M, Kubista M, Valihrach L. Cell Rep. 2020 Jun 16;31(11):107777. doi: 10.1016/j.celrep.2020.107777.

Abstract

Ischemic stroke is a well-recognized disease of aging, yet it is unclear how the age-dependent vulnerability occurs and what are the underlying mechanisms. To address these issues, we perform a comprehensive RNA-seq analysis of aging, ischemic stroke, and their interaction in 3- and 18-month-old mice. We assess differential gene expression across injury status and age, estimate cell type proportion changes, assay the results against a range of transcriptional signatures from the literature, and perform unsupervised co-expression analysis, identifying modules of genes with varying response to injury. We uncover downregulation of axonal and synaptic maintenance genetic program, and increased activation of type I interferon (IFN-I) signaling following stroke in aged mice. Together, these results paint a picture of ischemic stroke as a complex age-related disease and provide insights into interaction of aging and stroke on cellular and molecular level.