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 motor 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 insignificant motor neuron loss in the cortex, and likewise, 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 conclusively prove that the SOD1(G93A) mouse motor 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. Cerebral cortex of control (CTRL) and SOD1(G93A) mutant mice (SOD1) was isolated at four time points (1, 2, 3 and 4 months of age). Two males and two females were pooled per condition for preparation of cell suspension. The cell suspension was enriched for astrocytes, microglia and oligodendrocytes using FACS and was analysed by scRNA-seq (10X Genomics platform). Please note that transgenic mice expressing high levels of human SOD1(G93A) (JAX Strain: 004435 C57BL/6J-Tg (SOD1*G93A)1Gur/J) and their non-carrier littermates are used in the study.