Cortical glia in SOD1(G93A) mice are subtly affected by ALS-like pathology
Abstract 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. U...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2023-04-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-023-33608-y |
| _version_ | 1797841022803247104 |
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| author | Tereza Filipi Zuzana Matusova Pavel Abaffy Ondrej Vanatko Jana Tureckova Sarka Benesova Monika Kubiskova Denisa Kirdajova Jakub Zahumensky Lukas Valihrach Miroslava Anderova |
| author_facet | Tereza Filipi Zuzana Matusova Pavel Abaffy Ondrej Vanatko Jana Tureckova Sarka Benesova Monika Kubiskova Denisa Kirdajova Jakub Zahumensky Lukas Valihrach Miroslava Anderova |
| author_sort | Tereza Filipi |
| collection | DOAJ |
| description | Abstract 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. |
| first_indexed | 2024-04-09T16:24:09Z |
| format | Article |
| id | doaj.art-a35f615333f640c2a67600c1ef38b273 |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-04-09T16:24:09Z |
| publishDate | 2023-04-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-a35f615333f640c2a67600c1ef38b2732023-04-23T11:17:13ZengNature PortfolioScientific Reports2045-23222023-04-0113111510.1038/s41598-023-33608-yCortical glia in SOD1(G93A) mice are subtly affected by ALS-like pathologyTereza Filipi0Zuzana Matusova1Pavel Abaffy2Ondrej Vanatko3Jana Tureckova4Sarka Benesova5Monika Kubiskova6Denisa Kirdajova7Jakub Zahumensky8Lukas Valihrach9Miroslava Anderova10Department of Cellular Neurophysiology, Institute of Experimental Medicine, Czech Academy of SciencesLaboratory of Gene Expression, Institute of Biotechnology CAS, BIOCEVLaboratory of Gene Expression, Institute of Biotechnology CAS, BIOCEVDepartment of Cellular Neurophysiology, Institute of Experimental Medicine, Czech Academy of SciencesDepartment of Cellular Neurophysiology, Institute of Experimental Medicine, Czech Academy of SciencesLaboratory of Gene Expression, Institute of Biotechnology CAS, BIOCEVDepartment of Cellular Neurophysiology, Institute of Experimental Medicine, Czech Academy of SciencesDepartment of Cellular Neurophysiology, Institute of Experimental Medicine, Czech Academy of SciencesDepartment of Functional Organization of Biomembranes, Institute of Experimental Medicine, Czech Academy of SciencesLaboratory of Gene Expression, Institute of Biotechnology CAS, BIOCEVDepartment of Cellular Neurophysiology, Institute of Experimental Medicine, Czech Academy of SciencesAbstract 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.https://doi.org/10.1038/s41598-023-33608-y |
| spellingShingle | Tereza Filipi Zuzana Matusova Pavel Abaffy Ondrej Vanatko Jana Tureckova Sarka Benesova Monika Kubiskova Denisa Kirdajova Jakub Zahumensky Lukas Valihrach Miroslava Anderova Cortical glia in SOD1(G93A) mice are subtly affected by ALS-like pathology Scientific Reports |
| title | Cortical glia in SOD1(G93A) mice are subtly affected by ALS-like pathology |
| title_full | Cortical glia in SOD1(G93A) mice are subtly affected by ALS-like pathology |
| title_fullStr | Cortical glia in SOD1(G93A) mice are subtly affected by ALS-like pathology |
| title_full_unstemmed | Cortical glia in SOD1(G93A) mice are subtly affected by ALS-like pathology |
| title_short | Cortical glia in SOD1(G93A) mice are subtly affected by ALS-like pathology |
| title_sort | cortical glia in sod1 g93a mice are subtly affected by als like pathology |
| url | https://doi.org/10.1038/s41598-023-33608-y |
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