Figure 7.

Pathological tau increases mitochondrial superoxide in TERT^−/− neurons. A, A high proportion of P301L-transduced neurons are labeled with AT8 (green; left). The optimal transduction efficiency was determined using a fluorescent reporter lentivirus. Neurons transduced with lentivirus-containing 53BP1-mCherry were γ-irradiated to induce DNA damage. The majority of cells were transduced, as indicated by the nuclei containing 53BP1 foci (red; second panel). Untransduced neurons do not label with anti-AT8 antibody. B, C, Neurons from wild-type and TERT^−/− mice were transduced with either truncated tau (B) or mutated tau (C). Double-labeling with MitoSOX (red) and anti-AT8 (green) was conducted, and levels of superoxide were measured in three cell areas: the soma, apical dendrites, and basal dendrites. D, There were no differences in MitoSOX fluorescence between wild-type and TERT^−/− neurons transduced with truncated tau. E, MitoSOX fluorescence was increased in the dendrites of TERT^−/− neurons transduced with mutated tau. *p < 0.05 (one-way ANOVA with Tukey's post hoc test). Data are mean ± SEM from three independent experiments.