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• W2888099268 abstract "Dystrophin deficiency in mdx mice, a model for Duchenne muscular dystrophy, leads to muscle weakness revealed by a reduced specific maximal force as well as fragility (ie, higher susceptibility to contraction-induced injury, as shown by a greater force decrease after lengthening contractions). Both symptoms could be improved with dystrophin restoration–based therapies and long-term (months) voluntary exercise. Herein, we evaluated the effect of short-term (1-week) voluntary wheel running. We found that running improved fragility of tibialis anterior muscle (TA), but not plantaris muscle, independently of utrophin up-regulation, without affecting weakness. Moreover, TA muscle excitability was also preserved by running, as shown by compound muscle action potential measurements after lengthening contractions. Of interest, the calcineurin inhibitor cyclosporin A prevented the effect of running on both muscle fragility and excitability. Cyclosporin also prevented the running-induced changes in expression of genes involved in excitability (Scn4a and Cacna1s) and slower contractile phenotype (Myh2 and Tnni1) in TA muscle. In conclusion, short-term voluntary exercise improves TA muscle fragility in mdx mice, without worsening weakness. Its effect was related to preserved excitability, calcineurin pathway activation, and changes in the program of genes involved in excitability and slower contractile phenotype. Thus, remediation of muscle fragility of Duchenne muscular dystrophy patients through appropriate exercise training deserves to be explored in more detail. Dystrophin deficiency in mdx mice, a model for Duchenne muscular dystrophy, leads to muscle weakness revealed by a reduced specific maximal force as well as fragility (ie, higher susceptibility to contraction-induced injury, as shown by a greater force decrease after lengthening contractions). Both symptoms could be improved with dystrophin restoration–based therapies and long-term (months) voluntary exercise. Herein, we evaluated the effect of short-term (1-week) voluntary wheel running. We found that running improved fragility of tibialis anterior muscle (TA), but not plantaris muscle, independently of utrophin up-regulation, without affecting weakness. Moreover, TA muscle excitability was also preserved by running, as shown by compound muscle action potential measurements after lengthening contractions. Of interest, the calcineurin inhibitor cyclosporin A prevented the effect of running on both muscle fragility and excitability. Cyclosporin also prevented the running-induced changes in expression of genes involved in excitability (Scn4a and Cacna1s) and slower contractile phenotype (Myh2 and Tnni1) in TA muscle. In conclusion, short-term voluntary exercise improves TA muscle fragility in mdx mice, without worsening weakness. Its effect was related to preserved excitability, calcineurin pathway activation, and changes in the program of genes involved in excitability and slower contractile phenotype. Thus, remediation of muscle fragility of Duchenne muscular dystrophy patients through appropriate exercise training deserves to be explored in more detail. Duchenne muscular dystrophy (DMD) is a disorder affecting both skeletal and cardiac muscles, caused by dystrophin deficiency, a subsarcolemmal protein that plays a role in force transmission and sarcolemma stability.1Chan S. Head S.I. The role of branched fibres in the pathogenesis of Duchenne muscular dystrophy.Exp Physiol. 2011; 96: 564-571Crossref PubMed Scopus (49) Google Scholar, 2Gumerson J.D. Michele D.E. The dystrophin-glycoprotein complex in the prevention of muscle damage.J Biomed Biotechnol. 2011; 2011: 210797Crossref PubMed Scopus (71) Google Scholar, 3Lynch G.S. Role of contraction-induced injury in the mechanisms of muscle damage in muscular dystrophy.Clin Exp Pharmacol Physiol. 2004; 31: 557-561Crossref PubMed Scopus (37) Google Scholar Skeletal muscle of the dystrophin-deficient mdx mice, a murine model for DMD, exhibits weakness [ie, reduced specific maximal force (absolute maximal force generated relative to muscle cross-sectional area or weight)].4Dellorusso C. Crawford R.W. Chamberlain J.S. Brooks S.V. Tibialis anterior muscles in mdx mice are highly susceptible to contraction-induced injury.J Muscle Res Cell Motil. 2001; 22: 467-475Crossref PubMed Scopus (166) Google Scholar, 5Hayes A. Williams D.A. Beneficial effects of voluntary wheel running on the properties of dystrophic mouse muscle.J Appl Phys. 1996; 80: 670-679Crossref PubMed Scopus (98) Google Scholar, 6Pastoret C. Sebille A. Time course study of the isometric contractile properties of mdx mouse striated muscles.J Muscle Res Cell Motil. 1993; 14: 423-431Crossref PubMed Scopus (35) Google Scholar The mdx skeletal muscle is also more fragile [ie, susceptible to damage caused by lengthening (eccentric) contractions, which cause an immediate marked force decrease after lengthening contractions in fast low oxidative muscle in mdx mice, but not slow oxidative muscle].7Head S.I. Williams D.A. Stephenson D.G. Abnormalities in structure and function of limb skeletal muscle fibres of dystrophic mdx mice.Proc Biol Sci. 1992; 248: 163-169Crossref PubMed Scopus (111) Google Scholar, 8Moens P. Baatsen P.H. Marechal G. Increased susceptibility of EDL muscles from mdx mice to damage induced by contractions with stretch.J Muscle Res Cell Motil. 1993; 14: 446-451Crossref PubMed Scopus (263) Google Scholar, 9Petrof B.J. Shrager J.B. Stedman H.H. Kelly A.M. Sweeney H.L. Dystrophin protects the sarcolemma from stresses developed during muscle contraction.Proc Natl Acad Sci U S A. 1993; 90: 3710-3714Crossref PubMed Scopus (1176) Google Scholar Recently, it was found that reduced excitability (ie, plasmalemma electrical dysfunction) largely contributes to the immediate force decrease after lengthening contractions in mdx mouse muscle.10Roy P. Rau F. Ochala J. Messéant J. Fraysse B. Lainé J. Agbulut O. Butler-Browne G. Furling D. Ferry A. Dystrophin restoration therapy improves both the reduced excitability and the force drop induced by lengthening contractions in dystrophic mdx skeletal muscle.Skelet Muscle. 2016; 6: 23Crossref PubMed Scopus (19) Google Scholar These most important functional dystrophic features, weakness and fragility, are both rescued in mdx mice treated with dystrophin restoration–based therapies.10Roy P. Rau F. Ochala J. Messéant J. Fraysse B. Lainé J. Agbulut O. Butler-Browne G. Furling D. Ferry A. Dystrophin restoration therapy improves both the reduced excitability and the force drop induced by lengthening contractions in dystrophic mdx skeletal muscle.Skelet Muscle. 2016; 6: 23Crossref PubMed Scopus (19) Google Scholar, 11Dumonceaux J. Marie S. Beley C. Trollet C. Vignaud A. Ferry A. Butler-Browne G. Garcia L. Combination of myostatin pathway interference and dystrophin rescue enhances tetanic and specific force in dystrophic mdx mice.Mol Ther. 2010; 18: 881-887Abstract Full Text Full Text PDF PubMed Scopus (50) Google Scholar, 12Goyenvalle A. Griffith G. Babbs A. El Andaloussi S. Ezzat K. Avril A. Dugovic B. Chaussenot R. Ferry A. Voit T. Amthor H. Buhr C. Schurch S. Wood M.J. Davies K.E. Vaillend C. Leumann C. Garcia L. Functional correction in mouse models of muscular dystrophy using exon-skipping tricyclo-DNA oligomers.Nat Med. 2015; 21: 270-275Crossref PubMed Scopus (219) Google Scholar, 13Hoogaars W. Mouisel E. Pasternack A. Hulmi J.J. Relizani K. Schuelke M. Schirwis E. Garcia L. Ritvos O. Ferry A. t Hoen P.A. Amthor H. Combined effect of AAV-U7-induced dystrophin exon skipping and soluble activin type IIB receptor in mdx mice.Hum Gene Ther. 2012; 23: 1269-1279Crossref PubMed Scopus (30) Google Scholar, 14Koo T. Malerba A. Athanasopoulos T. Trollet C. Boldrin L. Ferry A. Popplewell L. Foster H. Foster K. Dickson G. Delivery of AAV2/9-microdystrophin genes incorporating helix 1 of the coiled-coil motif in the C-terminal domain of dystrophin improves muscle pathology and restores the level of alpha1-syntrophin and alpha-dystrobrevin in skeletal muscles of mdx mice.Hum Gene Ther. 2011; 22: 1379-1388Crossref PubMed Scopus (43) Google Scholar Moreover, we previously demonstrated that dystrophin restoration–based therapies in mdx mice reduce the force decrease after lengthening contractions via improved muscle excitability.10Roy P. Rau F. Ochala J. Messéant J. Fraysse B. Lainé J. Agbulut O. Butler-Browne G. Furling D. Ferry A. Dystrophin restoration therapy improves both the reduced excitability and the force drop induced by lengthening contractions in dystrophic mdx skeletal muscle.Skelet Muscle. 2016; 6: 23Crossref PubMed Scopus (19) Google Scholar Of interest, chronic muscular exercise can also improve functional dystrophic features.15Hyzewicz J. Ruegg U.T. Takeda S. Comparison of experimental protocols of physical exercise for mdx mice and Duchenne muscular dystrophy patients.J Neuromuscul Dis. 2015; 2: 325-342Crossref PubMed Scopus (31) Google Scholar, 16Lovering R.M. Brooks S.V. Eccentric exercise in aging and diseased skeletal muscle: good or bad?.J Appl Physiol (1985). 2014; 116: 1439-1445Crossref PubMed Scopus (43) Google Scholar In particular, long-term voluntary exercise–based studies (3 weeks to 13 months), using wheel running, reported increased specific maximal force in hind limb muscle of mdx mice.5Hayes A. Williams D.A. Beneficial effects of voluntary wheel running on the properties of dystrophic mouse muscle.J Appl Phys. 1996; 80: 670-679Crossref PubMed Scopus (98) Google Scholar, 17Call J.A. Voelker K.A. Wolff A.V. McMillan R.P. Evans N.P. Hulver M.W. Talmadge R.J. Grange R.W. Endurance capacity in maturing mdx mice is markedly enhanced by combined voluntary wheel running and green tea extract.J Appl Physiol (1985). 2008; 105: 923-932Crossref PubMed Scopus (79) Google Scholar, 18Call J.A. McKeehen J.N. Novotny S.A. Lowe D.A. Progressive resistance voluntary wheel running in the mdx mouse.Muscle Nerve. 2010; 42: 871-880Crossref PubMed Scopus (65) Google Scholar, 19Selsby J.T. Acosta P. Sleeper M.M. Barton E.R. Sweeney H.L. Long-term wheel running compromises diaphragm function but improves cardiac and plantarflexor function in the mdx mouse.J Appl Physiol (1985). 2013; 115: 660-666Crossref PubMed Scopus (29) Google Scholar One study also found that long-term voluntary running decreases the force decrease after lengthening contractions in mdx mouse muscle [ie, improves (reduces) fragility].20Hourde C. Joanne P. Medja F. Mougenot N. Jacquet A. Mouisel E. Pannerec A. Hatem S. Butler-Browne G. Agbulut O. Ferry A. Voluntary physical activity protects from susceptibility to skeletal muscle contraction-induced injury but worsens heart function in mdx mice.Am J Pathol. 2013; 182: 1509-1518Abstract Full Text Full Text PDF PubMed Scopus (35) Google Scholar The notion that long-term voluntary running is beneficial for hind limb muscle from mdx mice is also supported by the fact that several weeks of physical inactivity aggravates muscle weakness as well as susceptibility to contraction-induced damage.20Hourde C. Joanne P. Medja F. Mougenot N. Jacquet A. Mouisel E. Pannerec A. Hatem S. Butler-Browne G. Agbulut O. Ferry A. Voluntary physical activity protects from susceptibility to skeletal muscle contraction-induced injury but worsens heart function in mdx mice.Am J Pathol. 2013; 182: 1509-1518Abstract Full Text Full Text PDF PubMed Scopus (35) Google Scholar However, the following are not yet known: i) whether a shorter period (1 week) of voluntary running is also beneficial for functional dystrophic features, ii) whether the beneficial effect of voluntary running is related to improved muscle excitability, and iii) what the mechanisms are behind the beneficial effect of voluntary running. In the context of a possible therapy by chronic muscular exercise, it is important to know whether beneficial effects can be achieved with a shorter duration. A short duration of chronic muscular exercise should allow a better compliance of the patient to the therapy. Different signaling pathways are activated by exercise in heathy muscle, leading to beneficial muscle remodeling (ie, cellular and molecular muscle adaptations).21Booth F.W. Ruegsegger G.N. Toedebusch R.G. Yan Z. Endurance exercise and the regulation of skeletal muscle metabolism.Prog Mol Biol Transl Sci. 2015; 135: 129-151Crossref PubMed Scopus (70) Google Scholar, 22Gundersen K. Excitation-transcription coupling in skeletal muscle: the molecular pathways of exercise.Biol Rev Camb Philos Soc. 2010; 86: 564-600Crossref PubMed Scopus (173) Google Scholar, 23Schiaffino S. Sandri M. Murgia M. Activity-dependent signaling pathways controlling muscle diversity and plasticity.Physiology (Bethesda). 2007; 22: 269-278Crossref PubMed Scopus (200) Google Scholar, 24Yan Z. Okutsu M. Akhtar Y.N. Lira V.A. Regulation of exercise-induced fiber type transformation, mitochondrial biogenesis, and angiogenesis in skeletal muscle.J Appl Physiol (1985). 2011; 110: 264-274Crossref PubMed Scopus (211) Google Scholar Numerous studies support the notion that the muscle remodeling induced by chronic exercise, such as the promotion of slower and more oxidative muscle fibers, is dependent on the activation of the calcineurin pathway in healthy muscle.23Schiaffino S. Sandri M. Murgia M. Activity-dependent signaling pathways controlling muscle diversity and plasticity.Physiology (Bethesda). 2007; 22: 269-278Crossref PubMed Scopus (200) Google Scholar, 24Yan Z. Okutsu M. Akhtar Y.N. Lira V.A. Regulation of exercise-induced fiber type transformation, mitochondrial biogenesis, and angiogenesis in skeletal muscle.J Appl Physiol (1985). 2011; 110: 264-274Crossref PubMed Scopus (211) Google Scholar, 25Chin E.R. Olson E.N. Richardson J.A. Yang Q. Humphries C. Shelton J.M. Wu H. Zhu W. Bassel-Duby R. Williams R.S. A calcineurin-dependent transcriptional pathway controls skeletal muscle fiber type.Genes Dev. 1998; 12: 2499-2509Crossref PubMed Scopus (835) Google Scholar, 26Dunn S.E. Burns J.L. Michel R.N. Calcineurin is required for skeletal muscle hypertrophy.J Biol Chem. 1999; 274: 21908-21912Crossref PubMed Scopus (215) Google Scholar, 27Pandorf C.E. Jiang W.H. Qin A.X. Bodell P.W. Baldwin K.M. Haddad F. Calcineurin plays a modulatory role in loading-induced regulation of type I myosin heavy chain gene expression in slow skeletal muscle.Am J Physiol Regul Integr Comp Physiol. 2009; 297: R1037-R1048Crossref PubMed Scopus (19) Google Scholar, 28Parsons S.A. Millay D.P. Wilkins B.J. Bueno O.F. Tsika G.L. Neilson J.R. Liberatore C.M. Yutzey K.E. Crabtree G.R. Tsika R.W. Molkentin J.D. Genetic loss of calcineurin blocks mechanical overload-induced skeletal muscle fiber type switching but not hypertrophy.J Biol Chem. 2004; 279: 26192-26200Crossref PubMed Scopus (153) Google Scholar However, it is not yet known whether the beneficial effect of voluntary running in mdx mice is also related to the activation of the calcineurin pathway. Several studies support this hypothesis by showing that activation of the calcineurin pathway alleviates the dystrophic features in mdx muscle.29Chakkalakal J.V. Michel S.A. Chin E.R. Michel R.N. Jasmin B.J. Targeted inhibition of Ca2+/calmodulin signaling exacerbates the dystrophic phenotype in mdx mouse muscle.Hum Mol Genet. 2006; 15: 1423-1435Crossref PubMed Scopus (52) Google Scholar, 30Stupka N. Plant D.R. Schertzer J.D. Emerson T.M. Bassel-Duby R. Olson E.N. Lynch G.S. Activated calcineurin ameliorates contraction-induced injury to skeletal muscles of mdx dystrophic mice.J Physiol. 2006; 575: 645-656Crossref PubMed Scopus (55) Google Scholar, 31Stupka N. Schertzer J.D. Bassel-Duby R. Olson E.N. Lynch G.S. Stimulation of calcineurin Aalpha activity attenuates muscle pathophysiology in mdx dystrophic mice.Am J Physiol Regul Integr Comp Physiol. 2008; 294: R983-R992Crossref PubMed Scopus (33) Google Scholar, 32Chakkalakal J.V. Harrison M.-A. Carbonetto S. Chin E. Michel R.N. Jasmin B.J. Stimulation of calcineurin signaling attenuates the dystrophic pathology in mdx mice.Hum Mol Genet. 2004; 13: 379-388Crossref PubMed Scopus (107) Google Scholar In particular, the overexpression of active calcineurin in tibialis anterior (TA) muscle of mdx mice reduces the force decrease after lengthening contractions.30Stupka N. Plant D.R. Schertzer J.D. Emerson T.M. Bassel-Duby R. Olson E.N. Lynch G.S. Activated calcineurin ameliorates contraction-induced injury to skeletal muscles of mdx dystrophic mice.J Physiol. 2006; 575: 645-656Crossref PubMed Scopus (55) Google Scholar This result was associated with increased percentage of muscle fibers expressing the slowest myosin heavy chains (MHCs; MHC-1 and MHC-2a) with higher oxidative capacity and utrophin A protein level, a homolog to dystrophin.30Stupka N. Plant D.R. Schertzer J.D. Emerson T.M. Bassel-Duby R. Olson E.N. Lynch G.S. Activated calcineurin ameliorates contraction-induced injury to skeletal muscles of mdx dystrophic mice.J Physiol. 2006; 575: 645-656Crossref PubMed Scopus (55) Google Scholar, 32Chakkalakal J.V. Harrison M.-A. Carbonetto S. Chin E. Michel R.N. Jasmin B.J. Stimulation of calcineurin signaling attenuates the dystrophic pathology in mdx mice.Hum Mol Genet. 2004; 13: 379-388Crossref PubMed Scopus (107) Google Scholar The slow and more oxidative muscle fibers, which are less fragile and affected in mdx mice, express more utrophin A than the fast less oxidative muscle fibers,8Moens P. Baatsen P.H. Marechal G. Increased susceptibility of EDL muscles from mdx mice to damage induced by contractions with stretch.J Muscle Res Cell Motil. 1993; 14: 446-451Crossref PubMed Scopus (263) Google Scholar, 33Chakkalakal J.V. Stocksley M.A. Harrison M.A. Angus L.M. Deschenes-Furry J. St-Pierre S. Megeney L.A. Chin E.R. Michel R.N. Jasmin B.J. Expression of utrophin A mRNA correlates with the oxidative capacity of skeletal muscle fiber types and is regulated by calcineurin/NFAT signaling.Proc Natl Acad Sci U S A. 2003; 100: 7791-7796Crossref PubMed Scopus (109) Google Scholar, 34Banks G.B. Combs A.C. Odom G.L. Bloch R.J. Chamberlain J.S. Muscle structure influences utrophin expression in mdx mice.PLoS Genet. 2014; 10: e1004431Crossref PubMed Scopus (26) Google Scholar and utrophin A is an effective surrogate for dystrophin in mdx muscles.35Deconinck N. Rafael J.A. Beckers-Bleukx G. Kahn D. Deconinck A.E. Davies K.E. Gillis J.M. Consequences of the combined deficiency in dystrophin and utrophin on the mechanical properties and myosin composition of some limb and respiratory muscles of the mouse.Neuromuscul Disord. 1998; 8: 362-370Abstract Full Text Full Text PDF PubMed Scopus (74) Google Scholar, 36Deconinck N. Tinsley J. De Backer F. Fisher R. Kahn D. Phelps S. Davies K. Gillis J.M. Expression of truncated utrophin leads to major functional improvements in dystrophin-deficient muscles of mice.Nat Med. 1997; 3: 1216-1221Crossref PubMed Scopus (212) Google Scholar, 37Squire S. Raymackers J.M. Vandebrouck C. Potter A. Tinsley J. Fisher R. Gillis J.M. Davies K.E. Prevention of pathology in mdx mice by expression of utrophin: analysis using an inducible transgenic expression system.Hum Mol Genet. 2002; 11: 3333-3344Crossref PubMed Scopus (129) Google Scholar Recently, it was demonstrated that the calcineurin pathway regulates utrophin A expression in skeletal muscle.33Chakkalakal J.V. Stocksley M.A. Harrison M.A. Angus L.M. Deschenes-Furry J. St-Pierre S. Megeney L.A. Chin E.R. Michel R.N. Jasmin B.J. Expression of utrophin A mRNA correlates with the oxidative capacity of skeletal muscle fiber types and is regulated by calcineurin/NFAT signaling.Proc Natl Acad Sci U S A. 2003; 100: 7791-7796Crossref PubMed Scopus (109) Google Scholar Our aim was to analyze the effect of short-term voluntary running, initiated at the age of 2 to 4 months, on hind limb muscle weakness and fragility of mdx mice. One week of voluntary running (wheel) improved susceptibility to damage caused by lengthening contractions in mdx mice. This improvement of muscle fragility was related to changes in muscle excitability. Finally, the calcineurin inhibitor, cyclosporin A (CsA), blocked the effect of voluntary running and prevented the changes in the expression of calcineurin-related genes, supporting the hypothesis that activation of the calcineurin pathway plays a role in the beneficial effect of short-term voluntary exercise in mdx mice. All procedures were performed in accordance with national and European legislations and were approved by our institutional Ethics Committee Charles Darwin (project 01362.02). The mdx mice (C57BL/10ScSc-DMDMdx/J; Mdx) and sex- and age-matched wild-type control mice (C57BL/10; C57) were used. Mice were randomly divided into different control and experimental groups. Mice at 2 to 4 months of age were placed in separate cages containing a wheel and were allowed to run 1 week ad libitum (Mdx + wheel). The running distances were collected. In addition, a group of mdx mice were exercised every day during 1 week on a horizontal motorized treadmill (5 minutes at 5 cm/second, 5 minutes at 10 cm/second, 5 minutes at 15 cm/second, and 45 minutes at 15 to 18 cm/second). In some experiments, mice were treated every day during 1 week with the calcineurin pathway inhibitor cyclosporine A (25 mg/kg, intraperitoneally, daily). Muscle weakness (reduced specific maximal force) and fragility (susceptibility to contraction-induced injury) were evaluated by measuring the in situ TA muscle contraction in response to nerve stimulation, as described previously.10Roy P. Rau F. Ochala J. Messéant J. Fraysse B. Lainé J. Agbulut O. Butler-Browne G. Furling D. Ferry A. Dystrophin restoration therapy improves both the reduced excitability and the force drop induced by lengthening contractions in dystrophic mdx skeletal muscle.Skelet Muscle. 2016; 6: 23Crossref PubMed Scopus (19) Google Scholar, 20Hourde C. Joanne P. Medja F. Mougenot N. Jacquet A. Mouisel E. Pannerec A. Hatem S. Butler-Browne G. Agbulut O. Ferry A. Voluntary physical activity protects from susceptibility to skeletal muscle contraction-induced injury but worsens heart function in mdx mice.Am J Pathol. 2013; 182: 1509-1518Abstract Full Text Full Text PDF PubMed Scopus (35) Google Scholar, 38Ferry A. Parlakian A. Joanne P. Fraysse B. Mgrditchian T. Roy P. Furling D. Butler-Browne G. Agbulut O. Mechanical overloading increases maximal force and reduces fragility in hind limb skeletal muscle from Mdx mouse.Am J Pathol. 2015; 185: 2012-2024Abstract Full Text Full Text PDF PubMed Scopus (9) Google Scholar In some experiments, extensor digitorum longus (EDL), gastrocnemius, and plantaris muscles were also studied. Mice were anesthetized using pentobarbital (60 mg/kg, intraperitoneally). Body temperature was maintained at 37°C using radiant heat. The knee and foot were fixed with pins and clamps, and the distal tendon of the muscle was attached to a lever arm of a servomotor system (305B, Dual-Mode Lever; Aurora Scientific, Aurora, ON, Canada) using a silk ligature. The sciatic nerve was proximally crushed and distally stimulated by a bipolar silver electrode using supramaximal square wave pulses of 0.1-millisecond duration. The absolute maximal force that was generated during isometric contractions in response to electrical stimulation (frequency of 75 to 150 Hz, train of stimulation of 500 milliseconds) was measured. Absolute maximal force was determined at L0 (length at which maximal tension was obtained during the tetanus). Absolute maximal force was normalized to the muscle mass as an estimate of specific maximal force, an index of muscle weakness. Fragility (ie, susceptibility to contraction-induced injury in mdx mice) was estimated from the force decrease resulting from lengthening contraction–induced injury. The sciatic nerve was stimulated for 700 milliseconds (frequency of 150 Hz). A maximal isometric contraction of the TA muscle was initiated during the first 500 milliseconds. Then, muscle lengthening (10% L0) at a velocity of 5.5 mm/second (0.85 fiber length/second) was imposed during the last 200 milliseconds. All isometric contractions were made at an initial length L0. Nine lengthening contractions of the TA muscles were performed in mdx mice, each separated by a 60-second rest period. Because the susceptibility to contraction-induced injury is lower in C57 mice,7Head S.I. Williams D.A. Stephenson D.G. Abnormalities in structure and function of limb skeletal muscle fibres of dystrophic mdx mice.Proc Biol Sci. 1992; 248: 163-169Crossref PubMed Scopus (111) Google Scholar, 8Moens P. Baatsen P.H. Marechal G. Increased susceptibility of EDL muscles from mdx mice to damage induced by contractions with stretch.J Muscle Res Cell Motil. 1993; 14: 446-451Crossref PubMed Scopus (263) Google Scholar in an experiment, C57 mice performed 18 lengthening contractions. The first nine lengthening contractions were similar as for mdx mice, but the muscle lengthening was greater (20% L0) during the nine last lengthening contractions. Maximal isometric force was measured 1 minute after each lengthening contraction and expressed as a percentage of the initial maximal force. After contractile measurements, the animals were sacrificed with cervical dislocation. For compound muscle action potential (CMAP) recordings, two monopolar needle electrodes were inserted into the belly of the TA muscle.10Roy P. Rau F. Ochala J. Messéant J. Fraysse B. Lainé J. Agbulut O. Butler-Browne G. Furling D. Ferry A. Dystrophin restoration therapy improves both the reduced excitability and the force drop induced by lengthening contractions in dystrophic mdx skeletal muscle.Skelet Muscle. 2016; 6: 23Crossref PubMed Scopus (19) Google Scholar The recording (cathode) and the reference (anode) electrodes were inserted into the proximal and the distal portion of the muscle, respectively. A third monopolar electrode was inserted in the contralateral hind limb muscle to ground the system. Data were amplified (BioAmp; ADInstruments, Sydney, NSW, Australia), acquired with a sampling rate of 100 kHz, and filtered at 5 kHz low pass and 1 Hz high pass (Powerlab 4/25; ADInstruments). Recording electrodes were positioned to achieve maximal CMAP amplitude. CMAPs were recorded during lengthening contractions, and the root mean square of the CMAP was calculated, as an index of CMAP amplitude. The root mean square of each CMAP corresponding to each contraction was then expressed as a percentage of the first contraction, used as a marker of muscle excitability. Muscles (TA and plantaris) were snap frozen in liquid nitrogen and stored at −80°C until use. Total RNA was isolated from TA and plantaris muscle tissues using Trizol (Invitrogen, Carlsbad, CA). cDNA was then synthesized from 1 μg of total RNA using the RevertAid First Strand cDNA Synthesis kit with random hexamers, according to the manufacturer's instructions (Thermo Fisher Scientific, Waltham, MA). RT-PCR was performed on a LightCycler 480 System at the platform iGenSeq of the Brain and Spinal Cord Institute, using LightCycler 480 SYBR Green I Master Mix (Roche, Basel, Switzerland).39Ferry A. Joanne P. Hadj-Said W. Vignaud A. Lilienbaum A. Hourdé C. Medja F. Noirez P. Charbonnier F. Chatonnet A. Chevessier F. Nicole S. Agbulut O. Butler-Browne G. Advances in the understanding of skeletal muscle weakness in murine models of diseases affecting nerve-evoked muscle activity, motor neurons, synapses and myofibers.Neuromuscul Disord. 2014; 24: 960-972Abstract Full Text Full Text PDF PubMed Scopus (9) Google Scholar The expressions of succinate dehydrogenase complex flavoprotein subunit A and hydroxymethylbilane synthase were used as reference transcripts. All sequences of primers used are presented in Table 1.Table 1Sequences of Primers UsedGeneForward primerReverse primerHousekeeping gene Sdha5′-TTACAAAGTGCGGGTCGATG-3′5′-GTGTGCTTCCTCCAGTGTTC-3′ Hmbs5′-AGGTCCCTGTTCAGCAAGAA-3′5′-TGGGCTCCTCTTGGAATGTT-3′Genes of interest Atp1a25′-GAAGGAGGTTGCCATGGATGA-3′5′-AGAATGTCCTGAGCTCGCTG-3′ Cacna15′-CCTCATCAGCAAGAAGCAGG-3′5′-TATGACAGACAGACCCTGGC-3′ Clcn15′-GACAACCCTGCACAAGACTC-3′5′-AAGACACCTCTGAGCTTCCC-3′ Cmya55′-TGGGTGATGGCTGTCAACTT-3′5′-TGTGGACGGTGCTGTTCTAAA-3′ Col1a15′-ATTCCCGTTCGAGTACGGAA-3′5′-CTCGATCTCGTTGGATCCCT-3′ Il1B5′-AAGGAGAACCAAGCAACGAC-3′5′-CTTGGGATCCACACTCTCCAG-3′ Myog5′-GAGCTATCCGGTTCCAAAGC-3′5′-TTCCCGGTATCATCAGCACA-3′ Myh25′-AAGCGAAGAGTAAGGCTGTC-3′5′-GTGATTGCTTGCAAAGGAAC-3′ Myh35′-TGAGCAAGACCTCCTGGTG-3′5′-TGCATGTGGAAAAGTGATACG-3′ Myh45′-ACAAGCTGCGGGTGAAGAGC-3′5′-CAGGACAGTGACAAAGAACG-3′ Myh75′-AGGTGTGCTCTCCAGAATGG-3′5′-CAGCGGCTTGATCTTGAAGT-3′ Myoz15′-TTGGCATTGACCTACTGGCAT-3′5′-GGCATTGCTGTCCTGTTGAAG-3′ Ncx15′-GGAGACTGCTCGTGTGTCTA-3′5′-TGTTGGTTGGCCTGAGAGAT-3′ Nduf55′-TTTCCGAAGACTGTCGCTCC-3′5′-TGGGATTTCTGCAAGCTCGG-3′ Nrf15′-GCTGCAGGTCCTGTGGGAATGG-3′5′-GCTGTCTCTTTCGGATAGATGG-3′ Pgc1α5′-GCTCAAGCCAAACCAACA-3′5′-CAGTTCCAGAGAGTTCCACA-3′ Pgc1β5′-GGAGACTGCTCTGGAAGGTG-3′5′-GGAAGCTACTCTCGCCACTG-3′ Rcan15′-ATGGAGGAGGTGGATCTGC-3′5′-TTCAAATTTGGCCCGGCAC-3′ Rcan35′-GACCTAAGTGACCTGCCCAC-3′5′-TCGGGCTTGCTGAAGTTGAT-3′ Scn4a5′-GCAACCTGGTGGTCCTGAAT-3′5′-CAGCCCCAAGAGGAAGGTTT-3′ Sdhb5′-TGCCATTTACCGATGGGACC-3′5′-CAAGAGCCACAGATGCCTTC-3′ Tfam5′-TCCCCTCGTCTATCAGTCTTGT-3′5′-CCACAGGGCTGCAATTTTCC-3′ TGF15′-CTGCTTTAGAAATGTGCAGG-3′5′-CAGAAGTTAGCATTGTACCC-3′ TNF5′-TCTCATGCACCATCAAGGACT-3′5′-ACCACTCTCCCTTTGCAGAACTCA-3′ Tnni15′-CACGAGGACTAAACTAGGCACT-3′5′-AGCATGAGTTTACGGGAGGC-3′ Tnni25′-CCTGAAGAGTGTGATGCTCCA-3′5′-CTCAGATTCTCGGCGGCTTT-3′ Open table in a new tab TA muscle tissue samples were disrupted in a homogenizer (Psychotron NS-310EII; Microtec Co, Ltd, Chiba, Japan) in 100 μL of lysis buffer (7 mol/L urea, 2 mol/L thiourea, 2% CHAPS, and 50 mmol/L dithiothreitol). Samples were centrifuged at 20,000 × g for 30 minutes, and the supernatant was stored at −20°C. Pro" @default.
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• W2888099268 date "2018-11-01" @default.
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• W2888099268 title "Improvement of Dystrophic Muscle Fragility by Short-Term Voluntary Exercise through Activation of Calcineurin Pathway in mdx Mice" @default.
• W2888099268 cites W1483410296 @default.
• W2888099268 cites W1487588756 @default.
• W2888099268 cites W1492569783 @default.
• W2888099268 cites W1504047759 @default.
• W2888099268 cites W1508397850 @default.
• W2888099268 cites W1549340072 @default.
• W2888099268 cites W1594995535 @default.
• W2888099268 cites W1771279210 @default.
• W2888099268 cites W1966029580 @default.
• W2888099268 cites W1970907481 @default.
• W2888099268 cites W1982152253 @default.
• W2888099268 cites W1982930017 @default.
• W2888099268 cites W1984196560 @default.
• W2888099268 cites W1987566334 @default.
• W2888099268 cites W1989689747 @default.
• W2888099268 cites W1993851978 @default.
• W2888099268 cites W2001380129 @default.
• W2888099268 cites W2003922674 @default.
• W2888099268 cites W2026362182 @default.
• W2888099268 cites W2035357444 @default.
• W2888099268 cites W2044437131 @default.
• W2888099268 cites W2047015778 @default.
• W2888099268 cites W2049504813 @default.
• W2888099268 cites W2052536416 @default.
• W2888099268 cites W2053152999 @default.
• W2888099268 cites W2062078686 @default.
• W2888099268 cites W2085648653 @default.
• W2888099268 cites W2095917282 @default.
• W2888099268 cites W2105484902 @default.
• W2888099268 cites W2106231162 @default.
• W2888099268 cites W2106898598 @default.
• W2888099268 cites W2109780125 @default.
• W2888099268 cites W2113931353 @default.
• W2888099268 cites W2117978515 @default.
• W2888099268 cites W2120747625 @default.
• W2888099268 cites W2121823236 @default.
• W2888099268 cites W2122679390 @default.
• W2888099268 cites W2124232812 @default.
• W2888099268 cites W2125410668 @default.
• W2888099268 cites W2135152055 @default.
• W2888099268 cites W2142330631 @default.
• W2888099268 cites W2142539012 @default.
• W2888099268 cites W2144099077 @default.
• W2888099268 cites W2145303230 @default.
• W2888099268 cites W2152252765 @default.
• W2888099268 cites W2153507951 @default.
• W2888099268 cites W2155028668 @default.
• W2888099268 cites W2157735441 @default.
• W2888099268 cites W2159443359 @default.
• W2888099268 cites W2162908178 @default.
• W2888099268 cites W2163605881 @default.
• W2888099268 cites W2169181364 @default.
• W2888099268 cites W2182162067 @default.
• W2888099268 cites W2271173630 @default.
• W2888099268 cites W2330409402 @default.
• W2888099268 cites W2423822803 @default.
• W2888099268 cites W2530771062 @default.
• W2888099268 cites W2569351015 @default.
• W2888099268 doi "https://doi.org/10.1016/j.ajpath.2018.07.015" @default.
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