Fig. 1: CPT1A P479L mice show resistance to chronic rotenone-induced motor and non-motor impairment and downregulation of CPT1 activity using etomoxir ameliorates rotenone-induced motor impairment.

a Male C57Bl/6J and CPT1A P479L mice received vehicle (carboxymethylcellulose sodium salt, 0.5%) or rotenone (30 mg/kg) for 32 days and were then evaluated by motor and non-motor behavior tests. b Male C57Bl/6J mice received vehicle (carboxymethylcellulose sodium salt, 0.5%) or rotenone (30 m/kg) for 32 days followed by an alternating treatment regime with etomoxir/vehicle and rotenone until termination at day 62. c Mean rounds per minute on the rotarod test (n = 10–18). d Mean normalized grip strength (n = 10–18). e Mean rounds per minute on the rotarod test at day 60 (n = 5–9). f Mean time to transverse the 0.6 cm beam at day 42 (n = 5–9). g Mean number of rears in the cylinder test (n = 9–17). h Time to descend the pole in the pole test (n = 3-6). i Mean weight of mice at day 62 in grams (n = 5–9). j Visuospatial memory based on the Y-maze test measured as mean spontaneous alternation percentage (n = 10–13). k Mean weight of mice at day 32 in grams (n = 5–18). Significant differences for behavior; *p ≤ 0.05; **p ≤ 0.01; ***p ≤ 0.001; ****p ≤ 0.0001. Wt wildtype, P479L Cpt1a P479L homozygote genotype, E etomoxir, R rotenone, V Vehicle, RPM rounds per minute, SAP spontaneous alternation percentage. Center line = mean, and whiskers = standard error of the mean except for i, center line = median and whiskers = interquartile range. Statistics: two-way or one-way ANOVA followed by Tukey post hoc test or Kruskal–Wallis test followed by Dunn post hoc test. We acknowledge Servier Medical Art for the mouse illustration, with the following license: https://creativecommons.org/licenses/by/3.0/. No changes were made to the drawing.