Fig. 3: IFNγ-mediated microglial activation triggers myelin damage.
From: T cell-mediated microglial activation triggers myelin pathology in a mouse model of amyloidosis
a, Image and quantification of OLIG2+ (green) EdU+ (gray) cells in the cortex of control or PLX-treated mice. ThR (red) indicate plaques. Unpaired two-sided Student’s t-test for n = 4 mice (control, PLX, *P = 0.03). b, SEM images and quantification of myelin abnormalities (green) in the cortex of control or PLX mice. Unpaired two-sided Student’s t-test for n = 3–4 mice (control, PLX, **P = 0.008). c, Image and quantification of CAII+ (green) Serpina3n+ (red) oligodendrocytes in the cortex of control or PLX mice. Unpaired two-sided Student’s t-test for n = 4–5 mice (control, PLX, **P = 0.0024). d, Schematic of the assay. e, Image showing IBA1+ (green) cells with internalized MBP (red). Quantification indicated fold change in the number of MBP+IBA1+ cells normalized to control. Left and middle: One-way ANOVA with Tukey’s post hoc test. Right, Unpaired two-sided Student’s t-test for n = 3–5 independent experiments (WT microglia, control, IFNγ, **P = 0.008; WT microglia, IFNγ, IFNγ + baricitinib, *P = 0.016; WT microglia, 5xFAD microglia, **P = 0.008; 5xFAD microglia, control, IFNγ + baricitinib, *P = 0.034; 5xFAD microglia, control, IFN1β, *P = 0.012; 5xFAD microglia, control, baricitinib, *P = 0.013). f, Image and quantification of OLIG2+ (green) EdU+ (gray) cells in the cortex of 7.5-month-old control or baricitinib-treated mice. ThR (red) indicate plaques. Unpaired two-sided Student’s t-test for n = 4–5 mice (control, baricitinib, *P = 0.047). g, SEM images and quantification of myelin abnormalities (green) in the cortex of 9-month-old control or baricitinib-treated mice. Unpaired two-sided Student’s t-test for n = 4 mice (control, baricitinib, **P = 0.002). h, Behavior of 5xFAD mice in the Barnes Maze after 12 weeks of treatment with baricitinib. Left: Tracing graphs in the platform trials in the Barnes maze. Right: Quantification of time in the target quadrant (%) on the platform during training and relative escape latency to the target hole in the probe trial. One-way ANOVA with Tukey’s post hoc analysis for n = 11–13 mice (relative escape latency, 12 weeks, WT control, 5xFAD control, ***P = 0.00000431; relative escape latency, 12 weeks, 5xFAD control, 5xFAD baricitinib, ***P = 0.00002349). Data are presented as the mean ± s.e.m. a,c,f, Scale bar, 10 µm. b,g, Scale bar, 1 µm.
