Fig. 2: SCDi infusion potently modulates gene expression in the 3xTg hippocampus, with main effects on immune- and synapse- related genes.

a Timeline of intracerebroventricular infusion experiment on the 9-month-old WT and 3xTg mice infused with either vehicle (DMSO) or SCD inhibitor (SCDi). Hippocampi were extracted after 1 month infusion and processed for whole hippocampus bulk RNA sequencing. b Principal component analysis of the four experimental groups using the whole transcriptome (“all genes”). c Heatmaps of the 777 DEGs (p ≤ 0.01) between WT-D and 3xTg-D groups, with DEG expression shown across the four treatment groups (n = 4 mice/group). d Venn diagram showing the overlap of the WT-D/3xTg-D and WT-D/3xTg-S DEG lists, in order to identify DEGs that are “Restored” (no longer significant), “Maintained” (still significant), or “New” (newly appearing) after SCDi infusion into 3xTg mice. e, f GO enrichment analysis showing the top 20 most enriched GO biological process gene sets for the “Restored” DEGs (e) and “New” DEGs (f) in SCDi-infused 3xTg mice. Restored gene were mainly enriched in GO Biological Process gene sets related to cellular response to stimuli, immunity and synapses (e) while the newly changed genes were mainly enriched in GO biological process gene sets related to nervous system development and synapses (f). See Supplemental Data File 2 for complete DEG lists.