Russell G. Rogers

Eccentric contractions disrupt FKBP12 content in mouse skeletal muscle

Strength deficits associated with eccentric contraction‐induced muscle injury stem, in part, from impaired voltage‐gated sarcoplasmic reticulum (SR) Ca2+ release. FKBP12 is a 12‐kD immunophilin known to bind to the SR Ca2+ release channel (ryanodine receptor, RyR1) and plays an important role in excitation‐contraction coupling. To assess the effects of eccentric contractions on FKBP12 content, we measured anterior crural muscle (tibialis anterior [TA], extensor digitorum longus [EDL], extensor hallucis longus muscles) strength and FKBP12 content in pellet and supernatant fractions after centrifugation via immunoblotting from mice before and after a single bout of either 150 eccentric or concentric contractions. There were no changes in peak isometric torque or FKBP12 content in TA muscles after concentric contractions. However, FKBP12 content was reduced in the pelleted fraction immediately after eccentric contractions, and increased in the soluble protein fraction 3 day after injury induction. FKBP12 content was correlated (P = 0.025; R2 = 0.38) to strength deficits immediately after injury induction. In summary, eccentric contraction‐induced muscle injury is associated with significant alterations in FKBP12 content after injury, and is correlated with changes in peak isometric torque.

Recovery of strength is dependent on mTORC1 signaling after eccentric muscle injury

Introduction: Eccentric contractions may cause immediate and long‐term reductions in muscle strength that can be recovered through increased protein synthesis rates. The purpose of this study was to determine whether the mechanistic target‐of‐rapamycin complex 1 (mTORC1), a vital controller of protein synthesis rates, is required for return of muscle strength after injury. Methods: Isometric muscle strength was assessed before, immediately after, and then 3, 7, and 14 days after a single bout of 150 eccentric contractions in mice that received daily injections of saline or rapamycin. Results: The bout of eccentric contractions increased the phosphorylation of mTORC1 (1.8‐fold) and p70s6k1 (13.8‐fold), mTORC1s downstream effector, 3 days post‐injury. Rapamycin blocked mTORC1 and p70s6k1 phosphorylation and attenuated recovery of muscle strength (∼20%) at 7 and 14 days. Conclusion: mTORC1 signaling is instrumental in the return of muscle strength after a single bout of eccentric contractions in mice. Muscle Nerve 54: 914–924, 2016

Recovery of skeletal muscle function following injury is not augmented by acute resveratrol supplementation

Background and Aim: Skeletal muscle function is significantly reduced following traumatic muscle injury and complete recovery can take several weeks. Pharmacological agents like nonsteroidal anti-inflammatory drugs have been used to minimize pain and inflammation associated with muscle injury. However, their safety and efficacy to improve muscle repair have been challenged. To that end, safer and more effective treatment options remain to be identified. Accordingly, resveratrol use has numerous health benefits in clinical population. Further, resveratrol has been shown to promote myoblast differentiation in0 vitro, which suggests it could be used to improve skeletal muscle regeneration in vivo. Methods: Experimental mice received resveratrol supplementation (0.05% wt/wt) 4 weeks prior to injury, which persisted throughout recovery. Muscle injury was induced by injecting a diluted barium chloride solution into the tibialis anterior (TA). Isometric tetanic and twitch torque of the anterior crural muscles were measured prior to the injury and 7, 14, or 21 days postinjury. Results: Resveratrol supplementation had no effect on preinjury isometric tetanic and twitch torque of the anterior crural muscles. Seven days after injury, tetanic torque production was reduced by 80% compared to preinjury values. Functional and structural recovery steadily improved at 14 days and was completed 21 days after injury. However, resveratrol treatment had no beneficial effects on isometric torque or regenerated fiber area. Conclusion: Acute, low-dose resveratrol supplementation did not improve functional or structural recovery of regenerating mouse TA after injury. Further research is likely required that explores alternate resveratrol dosing strategies and their effects on skeletal muscle repair processes.

Muscular strength is unaffected by short‑term resveratrol supplementation in aged mouse muscle

Background and Aim: Sarcopenia is the progressive loss of skeletal muscle mass and strength, due to aging. It represents a risk factor for physical frailty, reduced mobility, and increased incidence and severity of falls. Several biochemical mechanisms have been linked to sarcopenia such as aged-associated accumulation of oxidative damage that eventually can reduce muscular strength. Resveratrol supplementation has been shown to increase antioxidant content and reduce markers of oxidative stress and damage associated with age. However, the impact of resveratrol supplementation on functional deficits due to aging is less clear. Therefore, the aim of this brief investigation was to determine if short-term, low-to-moderate dose resveratrol supplementation would enhance strength in aged mouse skeletal muscle. Methods: In vivo anterior crural muscle function and tibialis anterior total antioxidant capacity were analyzed in 21-month-old C57BL/6 male mice after 7 weeks of being fed a control diet (n=10) of standard rodent chow or a treatment diet (n=10) of standard rodent chow supplemented with resveratrol (0.05% w/w). Results: The present study shows that 7 weeks of dietary resveratrol supplementation (0.05% w/w) did not alter twitch or peak isometric torque when compared with aged mice fed the control diet. Furthermore, resveratrol did not result in any detectable differences in the total antioxidant capacity of the tibialis anterior muscle. Conclusion: Short-term, low-to-moderate dose resveratrol supplementation does not appear to enhance in vivo anterior crural strength in aged mouse skeletal muscle. Key words: Aging, antioxidants, force, skeletal muscle, torque