Department of Cellular Neurophysiology, Institute of Experimental Medicine, Czech Academy of Sciences, Videnska 1083, 14220, Prague, Czech Republic.
Second Faculty of Medicine, Charles University, V Uvalu 84, 15006, Prague, Czech Republic.
Sci Rep. 2023 Apr 21;13(1):6538. doi: 10.1038/s41598-023-33608-y.
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.
胶质细胞在肌萎缩侧索硬化症（ALS）中的作用是不可否认的。它们与疾病相关的活性已在脊髓中得到广泛研究，但在大脑中仅部分得到研究。我们在此介绍了 SOD1(G93A) 小鼠大脑皮层中胶质细胞的全面研究 - 这是一种广泛使用的 ALS 模型。使用单细胞 RNA 测序（scRNA-seq）和免疫组织化学，我们在疾病的四个阶段检查了星形胶质细胞、小胶质细胞和少突胶质细胞，并考虑了性别的因素。我们报告称，无论疾病进展和性别如何，胶质细胞的变化都很小。伪群体和单细胞分析显示，在小胶质细胞和少突胶质细胞的终末期存在与疾病相关的细微转录改变，这些改变得到了免疫组织化学的支持。因此，我们的数据支持 SOD1(G93A) 小鼠皮层不能重现患者疾病的假说，我们建议在未来的皮质 ALS 病理学研究中使用不同的模型。
