Cortical astroglia undergo transcriptomic dysregulation in the G93A SOD1 ALS mouse model

摘要

Astroglia are the most abundant glia cell in the central nervous system, playing essential roles in maintaining homeostasis. Key functions of astroglia include, but are not limited to, neurotransmitter recycling, ion buffering, immune modulation, neurotrophin secretion, neuronal synaptogenesis and elimination, and blood-brain barrier maintenance. In neurological diseases, it is well appreciated that astroglia play crucial roles in the disease pathogenesis. In amyotrophic lateral sclerosis (ALS), a motor neuron degenerative disease, astroglia in the spinal cord and cortex downregulate essential transporters, among other proteins, that exacerbate disease progression. Spinal cord astroglia undergo dramatic transcriptome dysregulation. However, in the cortex, it has not been well studied what effects glia, especially astroglia, have on upper motor neurons in the pathology of ALS. To begin to shed light on the involvement and dysregulation that astroglia undergo in ALS, we isolated pure grey-matter cortical astroglia and subjected them to microarray analysis. We uncovered a vast number of genes that show dysregulation at end-stage in the ALS mouse model, G93A SOD1. Many of these genes play essential roles in ion homeostasis and the Wnt-signaling pathway. Several of these dysregulated genes are common in ALS spinal cord astroglia, while many of them are unique. This database serves as an approach for understanding the significance of dysfunction& genes and pathways in cortical astroglia in the context of motor neuron disease, as well as determining regional astroglia heterogeneity, and providing insight into ALS pathogenesis.