Back to Search
Start Over
Contractile efficiency of dystrophic mdx mouse muscle: in vivo and ex vivo assessment of adaptation to exercise of functional end points.
- Source :
-
Journal of applied physiology (Bethesda, Md. : 1985) [J Appl Physiol (1985)] 2017 Apr 01; Vol. 122 (4), pp. 828-843. Date of Electronic Publication: 2017 Jan 05. - Publication Year :
- 2017
-
Abstract
- Progressive weakness is a typical feature of Duchenne muscular dystrophy (DMD) patients and is exacerbated in the benign mdx mouse model by in vivo treadmill exercise. We hypothesized a different threshold for functional adaptation of mdx muscles in response to the duration of the exercise protocol. In vivo weakness was confirmed by grip strength after 4, 8, and 12 wk of exercise in mdx mice. Torque measurements revealed that exercise-related weakness in mdx mice correlated with the duration of the protocol, while wild-type (WT) mice were stronger. Twitch and tetanic forces of isolated diaphragm and extensor digitorum longus (EDL) muscles were lower in mdx compared with WT mice. In mdx, both muscle types exhibited greater weakness after a single exercise bout, but only in EDL after a long exercise protocol. As opposite to WT muscles, mdx EDL ones did not show any exercise-induced adaptations against eccentric contraction force drop. qRT-PCR analysis confirmed the maladaptation of genes involved in metabolic and structural remodeling, while damage-related genes remained significantly upregulated and angiogenesis impaired. Phosphorylated AMP kinase level increased only in exercised WT muscle. The severe histopathology and the high levels of muscular TGF-β1 and of plasma matrix metalloproteinase-9 confirmed the persistence of muscle damage in mdx mice. Therefore, dystrophic muscles showed a partial degree of functional adaptation to chronic exercise, although not sufficient to overcome weakness nor signs of damage. The improved understanding of the complex mechanisms underlying maladaptation of dystrophic muscle paves the way to a better managment of DMD patients. NEW & NOTEWORTHY We focused on the adaptation/maladaptation of dystrophic mdx mouse muscles to a standard protocol of exercise to provide guidance in the development of more effective drug and physical therapies in Duchenne muscular dystrophy. The mdx muscles showed a modest functional adaptation to chronic exercise, but it was not sufficient to overcome the progressive in vivo weakness, nor to counter signs of muscle damage. Therefore, a complex involvement of multiple systems underlies the maladaptive response of dystrophic muscle.<br /> (Copyright © 2017 the American Physiological Society.)
- Subjects :
- Adenylate Kinase metabolism
Animals
Diaphragm metabolism
Diaphragm physiopathology
Disease Models, Animal
Male
Matrix Metalloproteinase 9 metabolism
Mice
Mice, Inbred C57BL
Mice, Inbred mdx
Muscle Strength physiology
Muscle Weakness metabolism
Muscle Weakness physiopathology
Muscle, Skeletal metabolism
Muscular Dystrophy, Animal metabolism
Muscular Dystrophy, Animal physiopathology
Muscular Dystrophy, Duchenne metabolism
Torque
Up-Regulation physiology
Adaptation, Physiological physiology
Muscle Contraction physiology
Muscle, Skeletal physiopathology
Muscular Dystrophy, Duchenne physiopathology
Physical Conditioning, Animal physiology
Subjects
Details
- Language :
- English
- ISSN :
- 1522-1601
- Volume :
- 122
- Issue :
- 4
- Database :
- MEDLINE
- Journal :
- Journal of applied physiology (Bethesda, Md. : 1985)
- Publication Type :
- Academic Journal
- Accession number :
- 28057817
- Full Text :
- https://doi.org/10.1152/japplphysiol.00776.2015