Duchenne muscular dystrophy (DMD) is one of the most common and severe forms of muscular dystrophy. Oxidative myofibre content, muscle vasculature architecture and exercise tolerance are impaired in DMD. Several studies have demonstrated that nutrient supplements ameliorate dystrophic features, thereby enhancing muscle performance.Here, we report that dietary supplementation with a specific branched-chain amino acid enriched mixture (BCAAem) increased the abundance of oxidative muscle fibres associated with increased muscle endurance in dystrophic mdx mice. Amelioration of the fatigue index in BCAAem-treated mdx mice was caused by a cascade of events in the muscle tissue, which were promoted by endothelial nitric oxide synthase (eNOS) activation and vascular endothelial growth factor (VEGF) expression. VEGF induction led to recruitment of bone marrow (BM)-derived endothelial progenitors (EPs), which increased the capillary density of dystrophic skeletal muscle. Functionally, BCAAem mitigated the dystrophic phenotype of mdx mice without inducing dystrophin protein expression or replacing the dystrophin-associated glycoprotein (DAG) complex in the membrane, which is typically lost in DMD. BCAAem supplementation could be an effective adjuvant strategy in DMD treatment.
|Titolo:||Supplementation with a selective amino acid formula ameliorates muscular dystrophy in mdx mice.|
TORRENTE, YVAN (Corresponding)
|Parole Chiave:||Estrogen-receptor-alpha; mouse skeletal-muscle; endothelial progenitor cells; nitric-oxide; growth-factor; gene-transfer; mitochondrial biogenesis; satellite cells; messenger-RNA; mutant mice|
|Settore Scientifico Disciplinare:||Settore MED/26 - Neurologia|
|Data di pubblicazione:||12-set-2018|
|Digital Object Identifier (DOI):||10.1038/s41598-018-32613-w|
|Appare nelle tipologie:||01 - Articolo su periodico|