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

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.

Keywords: RNA-seq; WGCNA; aging; axon; cerebral ischemia; gene expression; interferon; parvalbumin; stroke; synapse.