Oxidative stress mediates tau-induced neurodegeneration in Drosophila
J. Clin. Invest. Dora Dias-Santagata, et al. 117:236 doi:10.1172/JCI28769 [
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Figure 2Downregulation of Sod2 or of Trxr antioxidant activities increases neuronal cell death in a
Drosophila tauopathy model.
(
A–
D) TUNEL assay in 10-day-old transgenic fly brains. Apoptotic cells, absent in control animals (
A), were identified by TUNEL staining (arrows) in the brains of tau
R406W transgenic flies (
B) and were found to be more abundant in tau
R406W flies heterozygous for
TrxrΔ1 (
C) and for
Sod2n283 (
D). Scale bar: 10 μm. (
E) Neurodegeneration was significantly enhanced by partial inactivation of Trxr (***
P < 0.001) and Sod2 (***
P < 0.001) activities. The number of TUNEL-positive cells in the brains of 10-day-old tau
R406W-expressing flies was compared with that in age-matched controls, in
Sod2n283 and
TrxrΔ1 heterozygous animals, and in tau
R406W flies heterozygous for either
Sod2n283 or
TrxrΔ1. Data points represent the mean ± SEM. (
F–
K) Tau-induced toxicity was associated with neuronal cell death. TUNEL-positive cells (green fluorescence) were found to coexpress the neuronal cell marker elav (red fluorescence) (
F–
H) and did not colocalize with repo-positive glial cells (red fluorescence) (
I–
K). Arrowheads mark the location of TUNEL-positive cells. Scale bars: 5 μm.