Figure 12

Suppression of rotenone-induced behavioral dysfunction by DJ-1-binding compound-23. Rotenone (suspended in 0.5% CMC) was orally administered to C57BL/6 mice at a dose of 30 mg/kg per day for 56 days. In addition, we injected mice with vehicle (closed circles; 1% DMSO, n = 22) or comp-23 (open squares; 1 mg/kg i.p., n = 16) once a day for 56 days, 30 min before the oral administration of rotenone. The vehicle control mice (open circles; n = 8) were received 0.5% CMC (p.o.) and 1% DMSO (i.p.) for 56 days. (A) The rota-rod test was performed every week. The speed of the rotating rod was accelerated in a stepwise manner (2 r.p.m, steps at intervals of 30 sec). Mice that had received oral rotenone showed significant motor dysfunction. This rotenone-induced dysfunction was significantly restored by administration of comp-23. Significance: *P < 0.05, **P < 0.01, ***P < 0.001 vs. vehicle. †p < 0.05, ††p < 0.01, †††p < 0.001 vs rotenone alone. (B and C) Time-dependent changes in the percentage (%) of mice remaining on the rotating rod at 0 (B) and 56 days (C). Mice that had received oral rotenone showed significantly greater motor dysfunction than those that had received vehicle at 56 days (p = 0.0016 by the log-rank test, C). Rotenone-induced motor dysfunction was significantly restored by administration of comp-23 (p = 0.0019 by the log-rank test, C).