Duchenne Muscular Dystrophy: Experimental models on Physical Therapy

Gaiad, Thaís Peixoto; Araújo, Karla Patrícia Cardoso; Caromano, Fátima Aparecida; Ambrósio, Carlos Eduardo

doi:10.5772/30329

Cited by 3 publications

(1 citation statement)

References 82 publications

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“…Animal models for Duchenne muscular dystrophy (DMD) have brought significant insights in the field of therapeutic exercise prescription and preclinical standards measurements ( Aurora et al, 2014 ; Frinchi et al, 2014 ; Gaiad et al, 2012 ; Smythe and White, 2011 ). The mdx mouse is the most common animal model with genetic and biochemistry homology and its progression phenotype is considered moderate ( Vainzof et al, 2008 ).…”

Section: Introductionmentioning

confidence: 99%

Low-intensity training provokes adaptive extracellular matrix turnover of a muscular dystrophy model

et al. 2017

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Recommendations of therapeutic exercise in Duchenne muscular dystrophy are still controversial. The hypothesis that a low-intensity training (LIT) protocol leads to muscle adaptations on mdx mice model was tested. Dystrophic male mice with 8 weeks old were separated in exercised (mdxE, n= 8) and sedentary (mdxC, n= 8) groups. Wild-type mice were used as control (WT, n= 8) group. Exercised group underwent a LIT protocol (9 m/min, 30 min, 3 days/wk, 60 days) on a horizontal treadmill. At day 60 all animals were analyzed regarding parameters of markers of muscle lesion and extracellular matrix turnover of muscle tissue by collagens fibers on tibial anterior muscle. Histomorphometry attested that centrally located nuclei fibers and the coefficient of variance of minimal Feret’s diameter was similar in mdxE and mdxC groups (P= 1.000) and both groups presented higher mean values than WT group (P< 0.001). Fraction area of collagen fibers of mdxE group was lower than mdxC group (P= 0,027) and similar to WT group (P= 0,751). Intramuscular area of Col3 of the mdxE group was higher than mdxC and WT groups (P<0.001). Intramuscular area of Col1 on the mdxE group was similar to the mdxC group (P= 1.000) and both groups were higher than WT group (P< 0.001). LIT protocol had not influenced muscle injuries resulting from the dystrophin-deficiency membrane fragility. Although, LIT had provoked adaptations on extracellular matrix bringing higher elastic feature to dystrophic muscle tissue.

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Section: Introductionmentioning

confidence: 99%

Low-intensity training provokes adaptive extracellular matrix turnover of a muscular dystrophy model

et al. 2017

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Bortezomib (PS-341) Treatment Decreases Inflammation and Partially Rescues the Expression of the Dystrophin-Glycoprotein Complex in GRMD Dogs

et al. 2013

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Golden retriever muscular dystrophy (GRMD) is a genetic myopathy corresponding to Duchenne muscular dystrophy (DMD) in humans. Muscle atrophy is known to be associated with degradation of the dystrophin-glycoprotein complex (DGC) via the ubiquitin-proteasome pathway. In the present study, we investigated the effect of bortezomib treatment on the muscle fibers of GRMD dogs. Five GRMD dogs were examined; two were treated (TD- Treated dogs) with the proteasome inhibitor bortezomib, and three were control dogs (CD). Dogs were treated with bortezomib using the same treatment regimen used for multiple myeloma. Pharmacodynamics were evaluated by measuring the inhibition of 20S proteasome activity in whole blood after treatment and comparing it to that in CD. We performed immunohistochemical studies on muscle biopsy specimens to evaluate the rescue of dystrophin and dystrophin-associated proteins in the muscles of GRMD dogs treated with bortezomib. Skeletal tissue from TD had lower levels of connective tissue deposition and inflammatory cell infiltration than CD as determined by histology, collagen morphometry and ultrastructural analysis. The CD showed higher expression of phospho-NFκB and TGF-β1, suggesting a more pronounced activation of anti-apoptotic factors and inflammatory molecules and greater connective tissue deposition, respectively. Immunohistochemical analysis demonstrated that dystrophin was not present in the sarcoplasmic membrane of either group. However, bortezomib-TD showed higher expression of α- and β-dystroglycan, indicating an improved disease histopathology phenotype. Significant inhibition of 20S proteasome activity was observed 1 hour after bortezomib administration in the last cycle when the dose was higher. Proteasome inhibitors may thus improve the appearance of GRMD muscle fibers, lessen connective tissue deposition and reduce the infiltration of inflammatory cells. In addition, proteasome inhibitors may rescue some dystrophin-associated proteins in the muscle fiber membrane.

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Motor Physical Therapy Affects Muscle Collagen Type I and Decreases Gait Speed in Dystrophin-Deficient Dogs

et al. 2014

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Golden Retriever Muscular Dystrophy (GRMD) is a dystrophin-deficient canine model genetically homologous to Duchenne Muscular Dystrophy (DMD) in humans. Muscular fibrosis secondary to cycles of degeneration/regeneration of dystrophic muscle tissue and muscular weakness leads to biomechanical adaptation that impairs the quality of gait. Physical therapy (PT) is one of the supportive therapies available for DMD, however, motor PT approaches have controversial recommendations and there is no consensus regarding the type and intensity of physical therapy. In this study we investigated the effect of physical therapy on gait biomechanics and muscular collagen deposition types I and III in dystrophin-deficient dogs. Two dystrophic dogs (treated dogs-TD) underwent a PT protocol of active walking exercise, 3×/week, 40 minutes/day, 12 weeks. Two dystrophic control dogs (CD) maintained their routine of activities of daily living. At t0 (pre) and t1 (post-physical therapy), collagen type I and III were assessed by immunohistochemistry and gait biomechanics were analyzed. Angular displacement of shoulder, elbow, carpal, hip, stifle and tarsal joint and vertical (Fy), mediolateral (Fz) and craniocaudal (Fx) ground reaction forces (GRF) were assessed. Wilcoxon test was used to verify the difference of biomechanical variables between t0 and t1, considering p<.05. Type I collagen of endomysium suffered the influence of PT, as well as gait speed that had decreased from t0 to t1 (p<.000). The PT protocol employed accelerates morphological alterations on dystrophic muscle and promotes a slower velocity of gait. Control dogs which maintained their routine of activities of daily living seem to have found a better balance between movement and preservation of motor function.

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Duchenne Muscular Dystrophy: Experimental models on Physical Therapy

Cited by 3 publications

References 82 publications

Low-intensity training provokes adaptive extracellular matrix turnover of a muscular dystrophy model

Low-intensity training provokes adaptive extracellular matrix turnover of a muscular dystrophy model

Bortezomib (PS-341) Treatment Decreases Inflammation and Partially Rescues the Expression of the Dystrophin-Glycoprotein Complex in GRMD Dogs

Motor Physical Therapy Affects Muscle Collagen Type I and Decreases Gait Speed in Dystrophin-Deficient Dogs

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