Fig. 4

Transcriptome analysis of striatal astrocytes after MACS via ACSA2 of MBP29-hα-syn mice. A Mosaic plot of altered astrocytic functions in the striatum of MBP29-hα-syn mice based on existing dataset assessed by Zamanian et al. [16]. Astrocytes display a distinct upregulation of transcripts linked to astrocyte reactivity. Notably, there is a strong enrichment in cytokine activity, extracellular matrix (ECM) organization, metabolic processes and transcription factor activity, as well as not clearly classifiable functions (Miscellaneous). B Volcano plot of differentially expressed genes (DEGs). DEGs were analyzed comparing MBP29-hα-syn mice with non-transgenic littermates. Thresholds were set to log2foldchange > 2.0 and adj. p value < 0.05. Y-axis: negative decade logarithm of adj. p value. X-axis: log2foldchange of gene expression levels. In turquoise: significantly downregulated genes, in grey: genes without statistical significance, in red: significantly upregulated genes. Top hits were marked with official gene symbols by the HUGO Gene Nomenclature Committee (HGNC). C, D Heatmap of the 20 most highly up- and downregulated genes according to adjusted p-value. Gene expression was scaled by rows to visualize differences in gene expression between and within the genotypes using log2foldchange of gene expression. Striatal astrocytes demonstrate a profound upregulation of pro-inflammatory transcripts. Additionally, homeostatic functions, such as lipid metabolism, calcium transport, and neurotransmitter signaling are impaired in astrocytes on transcriptional level. E, F Functional gene set enrichment analysis of DEGs (FDR > 0.05). Pathways are ordered by normalized enrichment score (NES). Nomenclature of pathways is modified from official hallmark and biological processes pathways. Bold: Pathways associated with pro-inflammatory pathways and impaired homeostasis