Figure 2.

Post-symptomatic AICAR improved running endurance and restored Complex IV activity and assembly in COX10-Mef2c mice. (A) Scheme of the post-symptomatic AICAR treatment. (B) Endurance measured as a function of time and represented in whisker plots. Cox10-Mef2c mice showed reduced endurance before the treatment started, age 4.5 m. AICAR-treatment during 3 months restored running endurance to control levels in the Cox10-Mef2c mice (age 7.5 m). The recovery was maintained for additional 4 months after the end of the treatment. Unpaired Student’s two-tailed t-test was performed and P values are shown. Significance was set at P < 0.05, (n ≥ 5 in all groups, with the exception of AICAR-treated Cox10-Mef2c mice of 11.5 months old were n = 3) (C-D) COX, SDH and COX/SDH histochemical double staining in cross sections of quadriceps. Arrows show COX-deficient fibers, which stain strongly for the SDH activity (blue) and weakly for the COX activity (light brown/white) (n = 5). (E) OXPHOS complex activities and citrate synthase activity expressed as percentage of the Control-vehicle group in homogenates from skeletal muscle (quadriceps). Data (n = 5) are presented as mean ± SEM, and unpaired Student’s two-tailed t-test was done for comparison of the two myopathy groups. (F) Steady-state levels of respiratory complexes in muscle homogenates from 7.5 month-old control and Cox10-Mef2c mice. Respiratory complexes in quadriceps (20 µg) from vehicle and AICAR-treated control and Cox10-Mef2c mice were separated by BN-PAGE (4–16% gels). (G) Quantification of BN-PAGE in (F) showing complexes levels normalized to SDH-A (CII) and to control animals.