Fig. 9: Microglia activation and expansion in a tauopathy mouse model is normalized upon the loss of Tuba4a C-terminal polyglutamylation.

A Western blot analysis of CD68 (marker for activated microglia) in cortical lysates derived from 12-month-old Tuba4a (WT) and Tuba4aΔpolyGlu mice crossed with a tauopathy mouse model (hTau (+/p)). Wild-type mice not expressing hTau, served as controls. B CD68 signal intensities normalized to γ-Adaptin, shown in (A). Tuba4a (WT) set to 1; n = 4 mice per genotype. C Iba1-positive cells (marker for microglia), in cortical brain sections derived from 12-month-old Tuba4a (WT) and Tuba4aΔpolyGlu mice, crossed with hTau (+/p) mice. Wild-type mice not expressing hTau, served as controls. Upper panels: Iba1 (greyscale) within layer V, scale bar, 50 µm. Middle and lower panels: magnification of boxed regions in upper panels; Iba1 (green), CD68 (red); scale bar, 25 µm. Lower panels: Sholl analysis with 6 µm intervals (circles). D Normalized cell number of Iba1-positive cells per area analyzed in cortical layer V. n = 6(WT), 8(+/+ and p/p) per genotype. E Quantification of Sholl analysis: the number of microglia branch intersections that occur from the soma in concentric circles was analyzed. Higher values reflect complex microglia processes, indicating activated microglia. Note that gliosis, as detectable in hTau cortical sections, is significantly reduced in the background of Tuba4aΔpolyGlu, as compared to Tuba4a (WT). n = 6(WT), 8(+/+ and p/p) per genotype. Two-sided one-way (B, D) or two-way (E; genotype × distance) ANOVA was used to assess statistical significance. *p < 0.05, **p < 0.01, ***p < 0.001. Data represent mean ± SEM. Source data, including exact p-values, are provided as a Source Data file.