Skeletal muscles in animal models of Duchenne muscular dystrophy (DMD) are more sensitive to contraction-induced functional loss, which is not related to fatigue. Valproic acid (VPA) is thought to improve serological and histological markers of damage in dystrophin-deficient murine muscles.
A French study involving researchers from the Institute tested the ability of VPA to reduce susceptibility to contraction-induced functional loss in two mouse models of DMD.
Adult female mdx (mildly affected) and D2-mdx (severely affected) mice were given VPA or a saline solution for 7 days. Some VPA-treated mdx mice also voluntarily ran in a wheel, which is known to reduce susceptibility to contraction-induced loss of function, i.e. the fall in isometric force after eccentric contractions. In situ muscle function was assessed before, during and after eccentric contractions. Muscle utrophin and desmin expression were also assessed by immunoblotting.
The results show that :
- VPA reduced the drop in isometric force after excentric contractions in both mouse models, with no change in relative maximal excentric force and utrophin and desmin expression.
- VPA for 7 days combined with voluntary running had no additive effect compared with VPA alone.
- VPA reduced absolute isometric peak force prior to excentric contractions in both mouse models.
These results indicate that VPA in both mouse models of DMD reduced susceptibility to contraction-induced functional loss but increased muscle weakness.
