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. 2020 Sep 14;10(25):11376–11403. doi: 10.7150/thno.49199

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SCI decreases transcriptional activity in the cortex related to neuronal synaptic function while long-term PLX depletion in the context of SCI increases astrocyte-related gene expression. (A) Table showing the number of differential expressed (DE) genes in the somatosensory cortex by pairwise comparison using NanoStringDiff. N = 4 mice/group. The three comparisons were as follows: (1) Sham/PLX vs. Sham/Veh; (2) SCI/Veh vs. Sham/Veh; and (3) SCI/PLX vs. SCI/Veh. About two-thirds of DE genes in the cortex after SCI were downregulated (SCI/Veh vs. Sham/Veh). PLX treatment in both Sham and SCI animals resulted in largely decreased expression of genes. (B) Distribution of DE genes in the cortex for the SCI/Veh vs. Sham/Veh comparison by pathway annotation. The neurons/neurotransmission and apoptosis pathways had the highest number of DE genes, with eight out of ten decreased in each category. Microglia function had the next highest number of DE genes as well as the highest number of genes with increased expression of any pathway (five). (C) Heatmap of DE genes in the cortex after SCI that are either downregulated (left; 30 genes) or upregulated (right; 14 genes). Color coding was based on z-score scaling. Individual tables show lists of DE genes by specific pathway. The “†” sign denotes genes that are upregulated. (D) Venn diagram showing the overlap of the DE gene lists for the three pairwise comparison. The central overlap area identifies five genes that are both modified by injury as well as PLX treatment after SCI and shown in the corresponding heatmap (color coding based on z-score scaling.) Two genes, Il1a and Lrrc25, were increased with injury in the cortex and decreased with PLX treatment. 68 genes were modified by PLX only in both Sham and SCI animals, and only two of these genes had increased expression (C4a, Slc2a1). A group of 17 genes were modified by PLX only in SCI animals. 11 out of 17 genes were increased in these animals relative to the SCI Veh group, and five of these upregulated genes were specifically associated with astrocyte function.