Continuous administration of poloxamer 188 reduces overload-induced muscular atrophy in dysferlin-deficient SJL mice

Dysferlin-deficient SJL mice are commonly used to study dysferlinopathy. We demonstrated that poloxamer 188 (P188), a membrane sealant, is effective in reducing the loss of muscle mass in SJL mice when administered using an osmotic pump for 6 weeks. We did not observe significant changes over a 2-week administration period, suggesting that longthier observation is necessary to determine the effectiveness of P188. We also examined exercise endurance in P188-administered SJL mice using a rolling cage. Phosphorylated p38 was found to be reduced in P188-administered SJL mice; additionally, using microarray analysis, we found diminished expression of atrogin-1, an E3 ubiquitin ligase, as the effector of muscular atrophy. Chronic infusion of P188 to dysferlin-deficient SJL mice reduced muscular atrophy, and administering p38 and atrogin-1 in the gastrocnemius muscle improved its motor function. These results provide a basis for potential treatments for dysferlin-deficient skeletal muscle fibers.

► P188 reduces overload-induced muscle atrophy in dysferlin-deficient mice.
► Phosphorylated p38 was reduced in P188 administered SJL mice.
► Diminished expression of atrogin-1, an E3-ubiquitin ligase, is the effector molecule.
► A basis for potential therapeutic strategies for dysferlinopathy.