Oxidative stress mediates tau-induced neurodegeneration in Drosophila
J. Clin. Invest. Dora Dias-Santagata, et al. 117:236 doi:10.1172/JCI28769 [Go to this article.]

Figure 1
Partial inactivation of antioxidant pathways enhances neurodegeneration in a Drosophila tauopathy model. (A–D) Frontal brain sections of 10-day-old flies were stained with H&E. Neurodegeneration was not detected in control flies (A) but was evident in transgenic flies expressing tau^R406W (B). Tau-induced toxicity was enhanced by removing 1 functional copy of Trxr in tau^R406W transgenic flies heterozygous for the Trxr^Δ1-null allele (C) and by reducing gene dosage of mitochondrial Sod2 in tau^R406W transgenic flies heterozygous for a null allele (Sod2ⁿ²⁸³) (D). Vacuolar degeneration was observed in the neuropil (arrows) and in the cortex (arrowheads). Scale bar: 20 μm. (E) Tau-induced toxicity was significantly enhanced by genetic downregulation of Trxr (***P < 0.001) and Sod2 (***P < 0.001) activities. Neurodegeneration was assessed by quantification of vacuoles with diameter greater than 3 μm in the brains of 10-day-old flies. Data points represent the mean ± SEM. In Figures 1, 2, and 7, genotypes are as follows: control, elav-GAL4/+; Trxr^Δ1, elav-GAL4/Trxr^Δ1; Sod2ⁿ²⁸³, elav-GAL4/+, Sod2ⁿ²⁸³/+; tau^R406W, elav-GAL4/+, UAS-tau^R406W/+; tau^R406W + Trxr^Δ1, elav-GAL4/Trxr^Δ1, UAS-tau^R406W/+; and tau^R406W + Sod2ⁿ²⁸³, elav-GAL4/+, Sod2ⁿ²⁸³/+, UAS-tau^R406W/+.