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

T. Filipi, Z. Matusova, P. Abaffy, O. Vanatko, J. Tureckova, S. Benesova, M. Kubiskova, D. Kirdajova, J. Zahumensky, L. Valihrach, M. Anderova

. 2023 ; 13 (1) : 6538. [pub] 20230421

Jazyk angličtina Země Anglie, Velká Británie

Typ dokumentu časopisecké články, práce podpořená grantem

Perzistentní odkaz   https://www.medvik.cz/link/bmc23011733

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.

Citace poskytuje Crossref.org

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$a The role of glia in amyotrophic lateral sclerosis (ALS) is undeniable. Their disease-related activity has been extensively studied in the spinal cord, but only partly in the brain. We present herein a comprehensive study of glia in the cortex of SOD1(G93A) mice-a widely used model of ALS. Using single-cell RNA sequencing (scRNA-seq) and immunohistochemistry, we inspected astrocytes, microglia, and oligodendrocytes, in four stages of the disease, respecting the factor of sex. We report minimal changes of glia throughout the disease progression and regardless of sex. Pseudobulk and single-cell analyses revealed subtle disease-related transcriptional alterations at the end-stage in microglia and oligodendrocytes, which were supported by immunohistochemistry. Therefore, our data support the hypothesis that the SOD1(G93A) mouse cortex does not recapitulate the disease in patients, and we recommend the use of a different model for future studies of the cortical ALS pathology.
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$a Matusova, Zuzana $u Laboratory of Gene Expression, Institute of Biotechnology CAS, BIOCEV, Prumyslova 595, 25250, Vestec, Czech Republic $u Faculty of Science, Charles University, Albertov 6, 12800, Prague, Czech Republic
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$a Abaffy, Pavel $u Laboratory of Gene Expression, Institute of Biotechnology CAS, BIOCEV, Prumyslova 595, 25250, Vestec, Czech Republic
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$a Kubiskova, Monika $u Department of Cellular Neurophysiology, Institute of Experimental Medicine, Czech Academy of Sciences, Videnska 1083, 14220, Prague, Czech Republic
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