Effects of prednisolone on skeletal muscle contractility in mdx mice.
Current treatment for Duchenne muscular dystrophy (DMD) is chronic administration of the glucocorticoid prednisolone. Prednisolone improves muscle strength in boys with DMD, but the mechanism is unknown. The purpose of this study was to determine how prednisolone improves muscle strength by examining muscle contractility in dystrophic mice over time and in conjunction with eccentric injury. Mdx mice began receiving prednisolone (n = 23) or placebo (n = 16) at 5 weeks of age. Eight weeks of prednisolone increased specific force of the extensor digitorum longus muscle 26%, but other parameters of contractility were not affected. Prednisolone also improved the histological appearance of muscle by decreasing the number of centrally nucleated fibers. Prednisolone treatment did not affect force loss during eccentric contractions or recovery of force following injury. These data are of clinical relevance, because the increase in muscle strength in boys with DMD taking prednisolone does not appear to occur via the same mechanism in dystrophic mice.
Baltgalvis
Kristen A
KA
Department of Biochemistry, University of Minnesota Medical School, 321 Church St. SE, Jackson Hall, 6-155, Minneapolis, Minnesota 55455, USA. kb@ddt.biochem.umn.edu
Call
Jarrod A
JA
Nikas
Jason B
JB
Lowe
Dawn A
DA
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D015992:Body Mass Index; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D016503:Drug Delivery Systems; D066298:In Vitro Techniques; D008297:Male; D051379:Mice; D018101:Mice, Inbred mdx; D009119:Muscle Contraction / Q000187:drug effects*; D018485:Muscle Fibers, Skeletal / Q000187:drug effects / Q000502:physiology; D053580:Muscle Strength; D018482:Muscle, Skeletal / Q000187:drug effects* / Q000503:physiopathology; D020388:Muscular Dystrophy, Duchenne / Q000473:pathology*; D009929:Organ Size / Q000187:drug effects; D011239:Prednisolone / Q000494:pharmacology*; D013997:Time Factors
D000893:Anti-Inflammatory Agents; D011239:Prednisolone