Fig. 2.

Rotenone rescues neuronal loss in two in vivo HD models. (A) A GFP reporter was coexpressed with mutant htt in the ASH neurons of C. elegans and was used to assess neuronal cell viability in vivo. Live neurons express GFP (arrow), and loss of GFP expression indicates cell death. (B) Rescue of age-dependent ASH neuronal death by rotenone (Rot). Animals were treated with DMSO (vehicle) or rotenone in the presence of food (left graph) or under starvation conditions (right graph). ASH neuronal viability was assayed in live animals at the time indicated. One hundred neurons (50 animals) were counted per treatment per time point, and the data are representative of two independent experiments. (C) Mutant htt expression in the photoreceptors of Drosophila results in a time-dependent degeneration. WT animals have seven visible-light-collecting units (rhabdomeres) per ommatidium when viewed by light microscopy. Mutant htt-expressing animals (Mut) show a decrease in the number of rhabdomeres at day 1 after eclosion (emergence as adults); progressive degeneration was age dependent after eclosion (SI Fig. 8). (D) HD flies were treated with vehicle (0.1% DMSO), rotenone, or sodium butyrate (NaB). Sodium butyrate (positive control) increased the number of visible rhabdomeres. The average number of rhabdomeres per ommatidium was calculated at 9 days posteclosion and is shown as a distribution. (See SI Fig. 8 for a dose–response experiment for rotenone.) Error bars represent one SE. *, The significant differences in the number of rhabdomeres between vehicle- and compound-treated animals were based on Student's t test (P < 0.05).