Cortical glia in SOD1(G93A) mice are subtly affected by ALS-like pathology

The role of glia in amyotrophic lateral sclerosis (ALS) is undeniable. Their disease-related activity has been extensively studied in the spinal cord, but only partly in the brain. We present herein a comprehensive study of glia in the cortex of SOD1(G93A) mice-a widely used model of ALS. Using single-cell RNA sequencing (scRNA-seq) and immunohistochemistry, we inspected astrocytes, microglia, and oligodendrocytes, in four stages of the disease, respecting the factor of sex. We report minimal changes of glia throughout the disease progression and regardless of sex. Pseudobulk and single-cell analyses revealed subtle disease-related transcriptional alterations at the end-stage in microglia and oligodendrocytes, which were supported by immunohistochemistry. Therefore, our data support the hypothesis that the SOD1(G93A) mouse cortex does not recapitulate the disease in patients, and we recommend the use of a different model for future studies of the cortical ALS pathology.

Automated summary

This study comprehensively investigates the disease-related activity of glia in the cortex of SOD1(G93A) mice using single-cell RNA sequencing and immunohistochemistry techniques. The results show minimal changes in glia throughout disease progression and regardless of sex. However, there were subtle disease-related transcriptional alterations in microglia and oligodendrocytes at the end-stage, supported by immunohistochemistry. Therefore, it is recommended to use a different model for future studies of the cortical ALS pathology.