Fig. 2: IL-12/Il-23 signaling reduces hippocampal oligodendrocytes in a mouse model of AD. | Nature Aging

Fig. 2: IL-12/Il-23 signaling reduces hippocampal oligodendrocytes in a mouse model of AD.

From: Interleukin-12 signaling drives Alzheimer’s disease pathology through disrupting neuronal and oligodendrocyte homeostasis

Fig. 2

a, Experimental outline. Isolated nuclei from hippocampi of 250-day-old animals (n = 3 per genotype), purified by FACS and used for snRNA-seq. Bulk RNA-seq libraries were prepared from RNA isolated of hippocampi (n = 3 per genotype). If not stated otherwise, figures reflect results from snRNA-seq. Illustration was created in BioRender: Geesdorf, M. (2025) https://BioRender.com/a60r345. b, UMAP plot showing 37 hippocampal cell clusters representing combined snRNA-seq data from three biological replicates per genotype. Cell types were assigned based on known markers. c, Cell type proportions in hippocampal samples across all three genotypes. Each dot represents one biological replicate (n = 3). One-way ANOVA with Holm–Bonferroni P value adjustment, df = 2. F = 1.945 for excitatory neurons, F = 0.563 for inhibitory neurons, F = 0.116 for astrocytes, F = 8.279 for microglia, F = 7.720 for oligodendrocytes and F = 2.245 for OPCs; boxplots show middle, median; lower hinge, 25% quantile; upper hinge, 75% quantile; upper/lower whisker, largest/smallest observation less/greater than or equal to upper/lower hinge ± 1.5× IQR. d, Mouse brain sections stained with DAPI (blue) and for Olig2 (red). The hippocampal outline was defined as the ROI (dashed white line) for quantifying Olig2+ cells. Scale bar, 100 µm. e, Representative zoomed-in images of brain tissue from WT, APPPS1 and APPPS1.Il12b−/− mice showing Olig2+ cells. f, Quantification of Olig2+ cells normalized to DAPI+ cells in hippocampal regions (n = 5 per genotype with 3–6 sections per animal). One-way ANOVA with Tukey’s multiple comparison test, df = 2, F = 6.270, *P = 0.0137. Each symbol represents one mouse. Bars represent mean ± s.e.m. g–i, Quantification of CC1+/Olig2+ mature oligodendrocytes in cortex, corpus callosum and CA1. n = 4 for WT and APPPS1 and n = 3 for APPPS1.Il12b−/− mice. Scale bar, 100 µm. g–i, One-way ANOVA with Tukey’s multiple comparison test on WT (mean = 91.67 ± s.e.m.), APPPS1 (mean = 77.99 ± s.e.m.) and APPPS1.Il12b−/− (mean = 94.87 ± s.e.m.), df = 2, F = 0.8176, *P = 0.0116 (g); WT (mean = 95.85 ± s.e.m.), APPPS1 (mean = 89.05 ± s.e.m.) and APPPS1.Il12b−/− (mean = 95.09 ± s.e.m.), df = 2, F = 7.132, *P = 0.0167 (h); WT (mean = 83.52 ± s.e.m.), APPPS1 (mean = 71.51 ± s.e.m.) and APPPS1.Il12b−/− (mean = 81.31 ± s.e.m.), df = 2, F = 10.04, **P = 0.0066. (i). df, degrees of freedom; IQR, interquartile range; NS, not significant.

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