Fig. 5. The microglia phenotype of females in CK-p25 model of neurodegeneration exhibit an earlier morphological shift than in males.

a, Sagittal view of analyzed brain regions with color coding. Timeline of degeneration events upon doxycycline withdrawal in the CK-p25 transgenic mouse model. b,c, UMAP plots displaying microglial morphological heterogeneity in adult control mice and CK-p25 mice at 1, 2 and 6 weeks after doxycycline withdrawal across all the analyzed brain regions for both sexes (b) or for each sex separately (c). Each dot represents a bootstrapped persistence image, and each UMAP highlights a distinct degeneration time point. n_samples = 500 per condition (‘Average and bootstrapped persistence images’). d, Representative confocal images of immunostained microglia (Iba1; green) and lysosomes (CD68; magenta) in CK-p25 mice at 1, 2 and 6 weeks after doxycycline withdrawal in FC, DG and S1. Scale bar, 10 μm. Palantir reconstruction of microglial trajectory (top) with corresponding color-coded average CD68 fold change (bottom) across three animals. Females, left. Males, right. Fold change < 0 in blue and > 0 in red.