Fig. 5
From: Activated cofilin exacerbates tau pathology by impairing tau-mediated microtubule dynamics
Cofilin mediates synaptic dysfunction in Tau-P301S mice. a Representative confocal images of synaptophysin (presynaptic, green) and drebrin (postsynaptic, red) in DIV21 hippocampal primary neurons derived from WT, Tau-P301S, and Tau-P301S;cofilin+/− littermates (scale bar = 20 μm). Rectangular white boxes highlight areas magnified in lower panels. b, c Quantification of synaptophysin and drebrin intensity in hippocampal primary neurons from WT, Tau-P301S, and Tau-P301S;cofilin+/− littermates. Data are expressed as mean ± SEM (one-way ANOVA with Tukey post hoc, n = 12–15/genotype, #p < 0.0001, ***p = 0.0005). d Confocal images showing increased synaptophysin (green) intensity in the hippocampus of Tau-P301S;cofilin+/− compared to Tau-P301S littermates. e Quantification of synaptophysin intensity in stratum lucidum (SL). Data are expressed as mean ± SEM (one-way ANOVA with Tukey post hoc, #p < 0.0001, n = 4 mice/genotype, scale bar = 100 μm). f–h Stimulating electrode placed in the Schaffer collaterals of the hippocampus and recording glass electrode positioned at the CA1 stratum radiatum below the pyramidal cell layer of acute slices. f Input/output analysis generated by stepping up stimulation amplitude from 1 to 15 mV in WT, Tau-P301S, and Tau-P301S;cofilin+/− acute slices. No significant differences observed. Data are expressed as mean ± SEM (WT: 30 slices, 4 mice; Tau-P301S: 31 slices, 4 mice; Tau-P301S;cofilin+/−: 29 slices, 4 mice). g PPF showing no significant differences across genotypes and interstimulus interval except between Tau-P301S;cofilin+/− and WT slices at the 40-ms interstimulus interval. Data are expressed as mean ± SEM (two-way ANOVA, post hoc Bonferroni, *p < 0.05; WT: 31 slices, 4 mice; Tau-P301S: 29 slices, 4 mice; Tau-P301S;cofilin+/−: 28 slices, 4 mice). h LTP induced by theta burst stimulation showing significant differences in fEPSP slope in Tau-P301S compared with WT and Tau-P301S;cofilin+/− slices at all time points. Data are expressed as mean ± SEM (two-way ANOVA, post hoc Bonferroni, p < 0.0001 at all time points, WT: 31 slices, 4 mice; Tau-P301S: 29 slices, 4 mice; Tau-P301S;cofilin+/−: 33 slices, 4 mice)
