Fig. 4: SCDi infusion rescues spine number and dendritic complexity in hippocampal neurons of 3xTg mice.

a–h Golgi staining in the hippocampus. Quantification of spine number on dentate gyrus (DG) (4 animals/group, average of 6–16 neurons/animal) (a, b) or CA1 neurons (4 animals/group, average of 6–14 neurons/animal) (c, d). In the DG, secondary dendrites were significantly decreased between WT-D/3xTg-D (p = 0.001) but not following SCDi treatment, WT-D/3xTg-S (p = 0.450) (a), and tertiary dendrites showed a trend towards a decrease between WT-D/3xTg-D (p = 0.111) but not following SCDi treatment, WT-D/3xTg-S (p = 0.857) (b). In CA1, secondary dendrites were significantly decreased between WT-D/3xTg-D (p = 0.007) but not following SCDi treatment, WT-D/3xTg-S (p = 0.993) (c), and tertiary dendrites were also significantly decreased between WT-D/3xTg-D (p = 0.011) but not following SCDi treatment, WT-D/3xTg-S (p = 0.847) (d). Two-way ANOVA, Dunnett’s post-hoc test. Quantification of the total dendritic length (e, g) or dendritic complexity (f, h) of neurons in the DG (4 animals per group, average of 6–16 neurons/animal) (e) or CA1 (4 animals per group, average of 4–13 neurons/animal) (g). Note a trend towards shorter dendrites between WT-D/3xTg-D (p = 0.086) that was not observed following SCDi treatment, WT-D/3xTg-S (p = 0.721). Sholl analysis of dendritic complexity in the DG (f) or CA1 (h) with box and whisker plots showing minimum, 1st quartile, median, 3rd quartile and maximum of area under the curve (AUC) (inset). Note a trend towards lower AUC between WT-D/3xTg-D (p = 0.0613) and not following SCDi treatment, WT-D/3xTg-S (p = 0.369) and a significant difference between WT-D/WT-S (p = 0.042). Two-way ANOVA, Dunnett’s post-hoc test. *p ≤ 0.05, **p ≤ 0.01. Error bars represent mean ± SEM. Scale bar, 5 μm. SCDi: Stearoyl-CoA desaturase inhibitor. i–j Immediate-early gene (IEG) expression in the hippocampus. Heatmap of the z-score of 18 IEGs (i). Violin plot of the 11 IEGs that are down-regulated between WT-D and 3xTg-D; note that expression of these 11 IEGs is significantly decreased between WT-D/3xTg-D (p = 0.0006) and upregulated to WT-D levels in 3xTg-S mice (WT-D/3xTg-S, p = 0.937), two-way ANOVA, Dunnett’s post-hoc test. (j). Violin plots represent minimum, 1st quartile, median, 3rd quartile and maximum. Error bars represent mean ± SEM. ***p ≤ 0.001 See Supplemental Data File 2 for synapse related DEG lists. Source data are provided as a Source Data file.