Fig. 4
From: Activated cofilin exacerbates tau pathology by impairing tau-mediated microtubule dynamics
Genetic reduction of cofilin mitigates tauopathy in Tau-P301S mice and tau-induced movement deficits in C. elegans. a, b Confocal images of PHF1 (pS396/404) and phospho-tau-pS199/pS202 in the hippocampus and cortex from WT, Tau-P301S, and Tau-P301S;cofilin+/− littermates, showing markedly reduced PHF1 and pS199/pS202 tau in Tau-P301S;cofilin+/− compared to Tau-P301S (scale bar = 20 μm). b Quantification of intensity for PHF1 (pS396/404) and pS199/pS202 tau in Tau-P301S, and Tau-P301S;cofilin+/− littermates in the cortex and hippocampus. Data are expressed as mean ± SEM (t-test, n = 4/genotype, #p < 0.0001) (scale bar = 20 μm). c–f Brain homogenates were prepared from 7-month-old WT, Tau-P301S, and Tau-P301S;cofilin+/− littermates. Representative immunoblots for sarkosyl-soluble and sarkosyl-insoluble tau, showing reduced sarkosyl-insoluble tau levels in Tau-P301S;cofilin+/− compared to Tau-P301S littermates. d, f Quantification of sarkosyl-soluble and sarkosyl-insoluble tau in WT, Tau-P301S, and Tau-P301S;cofilin+/− littermates. Data are expressed as mean ± SEM (one-way ANOVA with Tukey post hoc, n = 4/genotype, #p < 0.0001). g, h Motility (body length per second, BLPS) on NGM plates measured at ambient room temperature (22 °C) and normalized to N2 control from 40 to 50 worms per strain (scale bar = 0.2 mm). h Quantification of BLPS. Data are expressed as mean ± SEM (one-way ANOVA with Tukey post hoc, n = 40–50 worms/condition, #p < 0.0001). iC. elegans were subjected to qRT-PCR for the unc60 normalized to N2 control RNAi. Data are expressed as mean ± SEM (one-way ANOVA with Tukey post hoc, n = 40–50 worms/genotype, #p < 0.0001)
