Effects of prednisolone on skeletal muscle contractility in mdx mice

Abstract

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-wks of age. Eight wks of prednisolone increased specific force of the EDL 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.

Adaptive strength gains in dystrophic muscle exposed to repeated bouts of eccentric contraction

“…In vivo maximal isometric torque of the anterior crural muscles was assessed as previously described (3,7). Mice were anesthetized by an intraperitoneal injection of fentanyl citrate (10 mg/kg body wt), droperidol (0.2 mg/kg body wt), and diazepam (5 mg/kg body wt), and the left leg was shaved and aseptically prepared.…”

“…2. Maximal anterior crural muscle torques for bouts [1][2][3][4][5]. A: means Ϯ SE of peak isometric torques produced preinjury at bouts 1-5 for groups of mice with different rest intervals between bouts.…”

Microtubule binding distinguishes dystrophin from utrophin

“…This in vivo assay is designed to reveal more subtle differences between the WT, mdx, and transgenic mdx lines in resistance to more stringent mechanical stresses (48,49). Overall, the effect of genotype on torque loss was dependent on contraction number ( Fig.…”

Skeletal muscle contractile function and neuromuscular performance in Zmpste24 −/− mice, a murine model of human progeria

“…Passive torque about the left ankle joint was assessed by stabilizing the knee and placing the foot in a plate attached to a servomotor (300B-LR, Aurora Scientific, Aurora, Ontario, Canada) (Baltgalvis et al 2009;Garlich et al 2010). The servomotor rotated the ankle to four angles of dorsiflexion (5°, 10°, 15°, and 20°) and four angles of plantarflexion (5°, 10°, 15°, and 20°) and torque was measured at each angle.…”

“…Skeletal muscle contractility in vivo At 20 weeks of age, immediately following testing of joint mechanics and while still anesthetized, mice underwent in vivo contractile testing of the left leg (Baltgalvis et al 2009;Garlich et al 2010). First, maximal isometric torque of the anterior leg muscle group was measured by subdermal stimulation of the common peroneal nerve.…”