Fig. 1: Tideglusib treatment improves muscle performance, reduces muscle necrosis, and promotes the oxidative fiber type in 10–12-week-old and 28–30-week-old D2 mdx mice. | Nature Communications

Fig. 1: Tideglusib treatment improves muscle performance, reduces muscle necrosis, and promotes the oxidative fiber type in 10–12-week-old and 28–30-week-old D2 mdx mice.

From: GSK3 inhibition improves skeletal muscle function and whole-body metabolism in male mouse models of Duchenne muscular dystrophy

Fig. 1

a, b Tideglusib treatment increases twitch and tetanic (160 Hz) specific force production (mN/mm2) in the EDL muscle (10–12 weeks, vehicle n = 11, tideglusib n = 10; 28–30 weeks, vehicle n = 9, tideglusib n = 9). c, d Tideglusib treatment improves EDL muscle fatigue with a rightward shift in the fatigue curve in 10–12 week old mdx mice, but not in 28–30 week old mdx mice (10–12 weeks, vehicle n = 9, tideglusib n = 10; 28–30 weeks, vehicle n = 7, tideglusib n = 9). The fatigue protocol consisted of 70 Hz stimulation every 2 s for 160 s and force is presented as percent of initial force over time. e Hangwire impulse is lower in 28–30 week-old mdx mice compared to 10–12 week-old mdx mice, and greater with tideglusib treatment regardless of age (10–12 weeks, vehicle n = 10, tideglusib n = 10; 28–30 weeks, vehicle n = 9, tideglusib n = 8). f Serum creatine kinase (CK) levels are lower with tideglusib treatment and with age (10–12 weeks, vehicle n = 12, tideglusib n = 10; 28–30 weeks, vehicle n = 6, tideglusib n = 5). g, h Muscle histological analysis with H&E staining shows a significant reduction in % necrosis in EDL muscles obtained from 10 to 12 week old tideglusib treated mdx mice (n = 4 per group). Scale bar set to 200 μm. i–k Tideglusib treatment increases myofiber cross-sectional area (CSA) and the proportion of oxidative fibers (type I and IIA) in 10–12 week-old mdx mice (n = 4 per group). Blue, type I fibers; green, type IIA fibers; red, type IIB fibers; unstained (black), type IIX fibers. Scale bar set to 1000 μm. l Tideglusib treatment increases utrophin expression in mdx plantaris muscles from 10 to 12-week-old mdx mice (vehicle, n = 7 and tideglusib n = 10). m, n Tideglusib increases Pax7 and myogenin content in EDL muscles obtained from 28 to 30-week-old mdx mice (n = 6 per group for Pax7 and n = 5 per group for myogenin). For (a–f), a two-way ANOVA was used to assess the main effects of age or time and tideglusib treatment. Significant main effects are denoted in the text above. For (h, j–l and n), a two-tailed Student’s t-test was used. All values are mean ± SEM. *p < 0.05.

Back to article page