| Summary: | The administration of soluble ligand binding domain of type IIb activin receptor fused
to the Fc domain (sActRIIB-Fc) has been recently shown to attenuate dystrophic
pathology and to increase muscle mass, but also to supress aerobic metabolism. In
contrast, aerobic exercise is known for promoting aerobic capacity. The aim of the
present thesis was to investigate the effects of the combination of myostatin/activin
blocking and aerobic exercise on muscle gene expression profile of a in Duchenne
Muscular Dystrophy (DMD) model, the mdx mouse. Microarray analysis was
conducted from the gastrocnemius muscle and Gene Set Enrichement Analysis (GSEA)
was performed to examine the effects of the treatments and muscle dystrophy on gene
sets and pathways. The level of significance was set at False Discovery Rate (FDR) <
0.05.
The results indicate that the beneficial effects of exercise in dystrophic muscle induce
transcription responses towards the gene expression profile of the healthy muscle.
Furthermore, the combination of exercise with myostatin/activin inhibition combines
the benefits of each intervention alone, without any obvious side effect. The most
profound changes were observed in aerobic metabolism pathways, where the shift in
gene expression is presented in many different pathways. Moreover, the elevated
expressions in glutathione and drug metabolism by cytochrome P450 pathways suggest
a possible role for oxidative damage in DMD pathology and increases in BCAAs
degradation and lipid metabolism indicate a possible connection between these two
processes, but further research is needed to explore the role of oxidative damage in
DMD pathology and their possible connections.
|
|---|