Effects of Treadmill Exercise and High-Fat Feeding on Muscle Degeneration in Mdx Mice at the time of Weaning

1995 ◽  
Vol 89 (4) ◽  
pp. 447-452 ◽  
Author(s):  
Asghar Mokhtarian ◽  
Jean Pascal Lefaucheur ◽  
Patrick C. Even ◽  
Alain Sebille
Keyword(s):  
Motor Activity ◽  
Extensor Digitorum Longus ◽  
Treadmill Exercise ◽  
Extensor Digitorum ◽  
Mdx Mice ◽  
High Fat ◽  
Hindlimb Muscles ◽  
Muscle Necrosis ◽  
Muscle Energy Metabolism ◽  
Fat Feeding

1. Dystrophin-deficient hindlimb muscles of mdx mice undergo necrosis at the time of weaning when the motor activity of the mice greatly increases and muscle energy metabolism becomes more dependent on insulin and carbohydrates. 2. We have attempted to determine if the onset of myofibre necrosis in mdx mice at the time of weaning is related to the development of motor activity and/or the change in diet. 3. Fourteen-day-old mdx mice were divided into two groups after weaning. One group was trained to run on a treadmill and the other group was kept on a high-fat diet. Muscle necrosis was assessed histologically in the soleus and extensor digitorum longus muscles of mice in both experiments. 4. Keeping mice on a high-fat milk diet from the time of weaning up to 42 days of age did not influence the occurrence of necrosis in the soleus and extensor digitorum longus muscles of the mdx pups. In contrast, treadmill exercise greatly increased necrosis in both muscles. 5. We conclude that an increase in motor activity exacerbates the degeneration of hindlimb muscles of mdx mice at the time of weaning.

Glycogenesis in muscle and liver during exercise

1989 ◽  
Vol 66 (6) ◽  
pp. 2811-2817 ◽  
Author(s):  
C. A. Hutber ◽  
A. Bonen
Keyword(s):  
Extensor Digitorum Longus ◽  
Glycogen Synthesis ◽  
Extensor Digitorum ◽  
Glycogen Depletion ◽  
Hindlimb Muscles ◽  
Glucose Incorporation ◽  
White Gastrocnemius

We hypothesized that glycogenesis increases in muscle during exercise before significant glycogen depletion occurs. Therefore, rats ran for 15 or 90 min at speeds of 8–22 m/min. D-[5–3H]glucose (10 microCi/100 g body wt) was administered 10 min before the end of exercise. Hindlimb muscles [soleus (SOL), plantaris (PL), extensor digitorum longus (EDL), and red (RG) and white gastrocnemius (WG)] and a portion of liver were analyzed for glycogen concentrations and rates of glycogen synthesis (i.e., D-[3H]glucose incorporated into glycogen). At rest, marked differences were observed among muscles in their rates of glucose incorporation into glycogen: i.e., SOL = 24.3 +/- 3.1, RG = 5.4 +/- 1.9, PL = 2.8 +/- 1.1, EDL = 0.54 +/- 0.10, WG = 0.12 +/- 0.02 (SE) dpm.micrograms glycogen-1.10 min-1 (P less than 0.05 between respective muscles). Compared with the glucose incorporation into glycogen at rest, increments in the PL (272%), RG (189%), WG (400%), EDL (274%), and liver (175%) were observed after 90 min of exercise (P less than 0.05, all data). In contrast, a decrease in glucose incorporation into glycogen (-62%) occurred in the SOL at min 15 (P less than 0.05), but this returned to the rates observed at rest after 90 min of exercise. This measure for rates of net glycogen synthesis (dpm.microgram glycogen-1.10 min-1) was weakly related to the ambient glycogen levels in most muscles; the exception was the SOL (r = -0.79; P less than 0.05). There was up to a 50-fold difference in glycogen synthesis among muscles.(ABSTRACT TRUNCATED AT 250 WORDS)

scholarly journals Treadmill Exercise before and during Pregnancy Improves Bone Deficits in Pregnant Growth Restricted Rats without the Exacerbated Effects of High Fat Diet

Nutrients ◽  
2019 ◽  
Vol 11 (6) ◽  
pp. 1236
Author(s):  
Kristina Anevska ◽  
Dayana Mahizir ◽  
Jessica F. Briffa ◽  
Andrew J. Jefferies ◽  
John D. Wark ◽  
...  
Keyword(s):  
Treadmill Exercise ◽  
Quantitative Computed Tomography ◽  
Peripheral Quantitative Computed Tomography ◽  
High Fat ◽  
Plasma Analysis ◽  
Beneficial Effects ◽  
Uterine Vessel ◽  
Wistar Kyoto ◽  
Fat Feeding ◽  
Adult Bone

Growth restriction programs adult bone deficits and increases the risk of obesity, which may be exacerbated during pregnancy. We aimed to determine if high-fat feeding could exacerbate the bone deficits in pregnant growth restricted dams, and whether treadmill exercise would attenuate these deficits. Uteroplacental insufficiency was induced on embryonic day 18 (E18) in Wistar Kyoto (WKY) rats using bilateral uterine vessel ligation (restricted) or sham (control) surgery. The F1 females consumed a standard or high-fat (HFD) diet from 5 weeks, commenced treadmill exercise at 16 weeks, and they were mated at 20 weeks. Femora and plasma from the pregnant dams were collected at post-mortem (E20) for peripheral quantitative computed tomography (pQCT), mechanical testing, histomorphometry, and plasma analysis. Sedentary restricted females had bone deficits compared to the controls, irrespective of diet, where such deficits were prevented with exercise. Osteocalcin increased in the sedentary restricted females compared to the control females. In the sedentary HFD females, osteocalcin was reduced and CTX-1 was increased, with increased peak force and bending stress compared to the chow females. Exercise that was initiated before and continued during pregnancy prevented bone deficits in the dams born growth restricted, whereas a HFD consumption had minimal bone effects. These findings further highlight the beneficial effects of exercise for individuals at risk of bone deficits.

Contraction-induced injury to single permeabilized muscle fibers from mdx, transgenic mdx, and control mice

2000 ◽  
Vol 279 (4) ◽  
pp. C1290-C1294 ◽  
Author(s):  
Gordon S. Lynch ◽  
Jill A. Rafael ◽  
Jeffrey S. Chamberlain ◽  
John A. Faulkner
Keyword(s):  
Null Hypothesis ◽  
Fiber Length ◽  
Extensor Digitorum Longus ◽  
Muscle Fibers ◽  
Extensor Digitorum ◽  
Mdx Mice ◽  
And Control ◽  
Permeabilized Fibers ◽  
Permeabilized Muscle ◽  
Sarcolemmal Integrity

Muscle fibers of mdx mice that lack dystrophin are more susceptible to contraction-induced injury, particularly when stretched. In contrast, transgenic mdx (tg -mdx) mice, which overexpress dystrophin, show no morphological or functional signs of dystrophy. Permeabilization disrupts the sarcolemma of fibers from muscles of mdx, tg- mdx, and control mice. We tested the null hypothesis stating that, after single stretches of maximally activated single permeabilized fibers, force deficits do not differ among fibers from extensor digitorum longus muscles of mdx, tg -mdx, or control mice. Fibers were maximally activated by Ca2+ (pCa 4.5) and then stretched through strains of 10%, 20%, or 30% of fiber length ( L f) at a velocity of 0.5 L f/s. Immediately after each strain, the force deficits were not different for fibers from each of the three groups of mice. When collated with studies of membrane-intact fibers in whole muscles of mdx, tg -mdx, and control mice, these results indicate that dystrophic symptoms do not arise from factors within myofibrils but, rather, from disruption of the sarcolemmal integrity that normally provides protection from contraction-induced injury.

Increased submaximal insulin-stimulated glucose uptake in mouse skeletal muscle after treadmill exercise

2006 ◽  
Vol 101 (5) ◽  
pp. 1368-1376 ◽  
Author(s):  
Taku Hamada ◽  
Edward B. Arias ◽  
Gregory D. Cartee
Keyword(s):  
Skeletal Muscle ◽  
Insulin Sensitivity ◽  
Glucose Uptake ◽  
Extensor Digitorum Longus ◽  
Treadmill Exercise ◽  
Genetically Modified ◽  
Extensor Digitorum ◽  
Exercise Protocol ◽  
Mouse Skeletal Muscle ◽  
Prior Exercise

The primary purpose of this study was to determine the effect of prior exercise on insulin-stimulated glucose uptake with physiological insulin in isolated muscles of mice. Male C57BL/6 mice completed a 60-min treadmill exercise protocol or were sedentary. Paired epitrochlearis, soleus, and extensor digitorum longus (EDL) muscles were incubated with [3H]-2-deoxyglucose without or with insulin (60 μU/ml) to measure glucose uptake. Insulin-stimulated glucose uptake for paired muscles was calculated by subtracting glucose uptake without insulin from glucose uptake with insulin. Muscles from other mice were assessed for glycogen and AMPK Thr172 phosphorylation. Exercised vs. sedentary mice had decreased glycogen in epitrochlearis (48%, P < 0.001), soleus (51%, P < 0.001), and EDL (41%, P < 0.01) and increased AMPK Thr172 phosphorylation ( P < 0.05) in epitrochlearis (1.7-fold), soleus (2.0-fold), and EDL (1.4-fold). Insulin-independent glucose uptake was increased 30 min postexercise vs. sedentary in the epitrochlearis (1.2-fold, P < 0.001), soleus (1.4-fold, P < 0.05), and EDL (1.3-fold, P < 0.01). Insulin-stimulated glucose uptake was increased ( P < 0.05) ∼85 min after exercise in the epitrochlearis (sedentary: 0.266 ± 0.045 μmol·g−1·15 min−1; exercised: 0.414 ± 0.051) and soleus (sedentary: 0.102 ± 0.049; exercised: 0.347 ± 0.098) but not in the EDL. Akt Ser473 and Akt Thr308 phosphorylation for insulin-stimulated muscles did not differ in exercised vs. sedentary. These results demonstrate enhanced submaximal insulin-stimulated glucose uptake in the epitrochlearis and soleus of mice 85 min postexercise and suggest that it will be feasible to probe the mechanism of enhanced postexercise insulin sensitivity by using genetically modified mice.

Influence of spaceflight on rat skeletal muscle

1988 ◽  
Vol 65 (5) ◽  
pp. 2318-2325 ◽  
Author(s):  
T. P. Martin ◽  
V. R. Edgerton ◽  
R. E. Grindeland
Keyword(s):  
Atpase Activity ◽  
Extensor Digitorum Longus ◽  
Extensor Digitorum ◽  
Medial Gastrocnemius ◽  
Male Rats ◽  
Cross Sectional ◽  
Hindlimb Muscles ◽  
Wet Weight ◽  
Flight Muscles ◽  
Loss Of Mass

The size, succinate dehydrogenase (SDH) and alpha-glycerolphosphate dehydrogenase (GPD) activities, and alkaline myofibrillar adenosinetriphosphatase (ATPase) staining properties were determined from quantitative histochemical analyses of single fibers from five hindlimb muscles of six male rats exposed to a 7-day National Aeronautics and Space Administration spaceflight mission (SL-3). These same properties were determined in a group of ground-based control rats housed under simulated environmental conditions. The wet weight of each of the flight muscles was significantly reduced relative to control. However, the loss of mass varied from 36% in the soleus to 15% in the extensor digitorum longus. The cross-sectional areas of fibers in the flight muscles also were reduced, except for the dark ATPase fibers in the medial gastrocnemius. The greatest relative fiber atrophy occurred in the muscles with the highest proportion of light ATPase fibers. An increase in the percentage of dark ATPase fibers also was observed in flight muscles with a predominance of light ATPase fibers. Also, there was an increase in the biochemically determined myofibrillar ATPase activity of tissue sections of the flight soleus. No changes in histochemical or biochemical measures of ATPase activity were observed in the flight extensor digitorum longus. In general, the SDH activity of flight muscles was maintained, whereas GPD activity either was maintained or increased. Based on a metabolic profile of ATPase, SDH, and GPD, there was an increase in the proportion of fast oxidative-glycolytic fibers in some muscles.

scholarly journals The passive mechanical properties of the extensor digitorum longus muscle are compromised in 2- to 20-mo-old mdx mice

2011 ◽  
Vol 110 (6) ◽  
pp. 1656-1663 ◽  
Author(s):  
Chady H. Hakim ◽  
Robert W. Grange ◽  
Dongsheng Duan
Keyword(s):  
Extensor Digitorum Longus ◽  
Extensor Digitorum ◽  
Muscle Pathology ◽  
Mdx Mice ◽  
Myotendinous Junction ◽  
Muscle Rigidity ◽  
Dependent Manner ◽  
Stress Strain ◽  
Longus Muscle ◽  
Edl Muscle

Muscle rigidity and myotendinous junction (MTJ) deficiency contribute to immobilization in Duchenne muscular dystrophy (DMD), a lethal disease caused by the absence of dystrophin. However, little is known about the muscle passive properties and MTJ strength in a diseased muscle. Here, we hypothesize that dystrophin-deficient muscle pathology renders skeletal muscle stiffer and MTJ weaker. To test our hypothesis, we examined the passive properties of an intact noncontracting muscle-tendon unit in mdx mice, a mouse model for DMD. The extensor digitorum longus (EDL) muscle-tendon preparations of 2-, 6-, 14-, and 20-mo-old mdx and normal control mice were strained stepwisely from 110% to 160% of the muscle optimal length. The stress-strain response and failure position were analyzed. In support of our hypothesis, the mdx EDL preparation consistently developed higher stress before muscle failure. Postfailure stresses decreased dramatically in mdx but not normal preparations. Further, mdx showed a significantly faster stress relaxation rate. Consistent with stress-strain assay results, we observed significantly higher fibrosis in mdx muscle. In 2- and 6-mo-old mdx and 20-mo-old BL10 mice failure occurred within the muscle (2- to 14-mo-old BL10 preparations did not fail). Interestingly, in ≥14-mo-old mdx mice the failure site shifted toward the MTJ. Electron microscopy revealed substantial MTJ degeneration in aged but not young mdx mice. In summary, our results suggest that the passive properties of the EDL muscle and the strength of MTJ are compromised in mdx in an age-dependent manner. These findings offer new insights in studying DMD pathogenesis and developing novel therapies.

Hindlimb immobilization applied to 21-day-oldmdx mice prevents the occurrence of muscle degeneration

1999 ◽  
Vol 86 (3) ◽  
pp. 924-931 ◽  
Author(s):  
Asghar Mokhtarian ◽  
Jean Pascal Lefaucheur ◽  
Patrick C. Even ◽  
Alain Sebille
Keyword(s):  
Skeletal Muscle ◽  
Motor Activity ◽  
Skeletal Muscles ◽  
Extensor Digitorum Longus ◽  
Contralateral Side ◽  
Mdx Mouse ◽  
Mdx Mice ◽  
Muscle Degeneration ◽  
Limb Immobilization ◽  
Old Mice

Dystrophin-deficient skeletal muscles of mdx mice undergo their first rounds of degeneration-regeneration at the age of 14–28 days. This feature is thought to result from an increase in motor activity at weaning. In this study, we hypothesize that if the muscle is prevented from contracting, it will avoid the degenerative changes that normally occur. For this purpose, we developed a procedure of mechanical hindlimb immobilization in 3-wk-old mice to restrain soleus (Sol) and extensor digitorum longus (EDL) muscles in the stretched or shortened position. After a 14-day period of immobilization, the striking feature was the low percentage of regenerated (centronucleated) myofibers in Sol and EDL muscles, regardless of the length at which they were fixed, compared with those on the contralateral side (stretched Sol: 8.4 ± 6.5 vs. 46.6 ± 10.3%, P = 0.0008; shortened Sol: 1.2 ± 1.6 vs. 50.4 ± 16.4%, P = 0.0008; stretched EDL: 05 ± 0.5 vs. 32.9 ± 17.5%, P = 0.002; shortened EDL: 3.3 ± 3.1 vs. 34.7 ± 11.1%, P = 0.002). Total numbers of myofibers did not change with immobilization. This study shows that limb immobilization prevents the occurrence of the first round of myofiber necrosis in mdx mice and suggests that muscle contractions play a role in the skeletal muscle degeneration of dystrophin-deficient mdx mouse muscles.

Coexistence of twitch potentiation and tetanic force decline in rat hindlimb muscle

1988 ◽  
Vol 65 (6) ◽  
pp. 2687-2695 ◽  
Author(s):  
L. L. Rankin ◽  
R. M. Enoka ◽  
K. A. Volz ◽  
D. G. Stuart
Keyword(s):  
Fatigue Test ◽  
Extensor Digitorum Longus ◽  
Motor Units ◽  
Extensor Digitorum ◽  
Adult Rats ◽  
Twitch Force ◽  
Twitch Potentiation ◽  
Hindlimb Muscles ◽  
Hindlimb Muscle ◽  
Isometric Twitch

An experimental protocol designed to assess fatigability in motor units has been applied to two hindlimb muscles of anesthetized adult rats to study the effects of whole-muscle fatigue on the isometric twitch. Both soleus and extensor digitorum longus exhibited a linear relationship between fatigability (i.e., force decline after a 360-s fatigue test) and the magnitude of the twitch force following the fatigue test. Twitch force after the fatigue test was potentiated (i.e., greater than the value before the fatigue test) in many muscles, despite the development of considerable fatigue. This coexistence of fatigue and twitch potentiation was observed in 7% (5/70) of soleus and 48% (31/64) of extensor digitorum longus muscles. The coexistence was exhibited only by the least fatigable muscles of the fast-contracting extensor digitorum longus. The extensor digitorum longus muscles that did not exhibit twitch potentiation probably experienced a higher proportion of muscle-fiber inactivation, such as due to failure of neuromuscular propagation, that was induced by the fatigue regimen.

scholarly journals Long-term wheel running compromises diaphragm function but improves cardiac and plantarflexor function in the mdx mouse

2013 ◽  
Vol 115 (5) ◽  
pp. 660-666 ◽  
Author(s):  
Joshua T. Selsby ◽  
Pedro Acosta ◽  
Meg M. Sleeper ◽  
Elisabeth R. Barton ◽  
H. Lee Sweeney
Keyword(s):  
Cardiac Function ◽  
Endurance Training ◽  
Muscle Function ◽  
Extensor Digitorum Longus ◽  
Wheel Running ◽  
Extensor Digitorum ◽  
Mdx Mice ◽  
Limb Muscle ◽  
Specific Tension

Dystrophin-deficient muscles suffer from free radical injury, mitochondrial dysfunction, apoptosis, and inflammation, among other pathologies that contribute to muscle fiber injury and loss, leading to wheelchair confinement and death in the patient. For some time, it has been appreciated that endurance training has the potential to counter many of these contributing factors. Correspondingly, numerous investigations have shown improvements in limb muscle function following endurance training in mdx mice. However, the effect of long-term volitional wheel running on diaphragm and cardiac function is largely unknown. Our purpose was to determine the extent to which long-term endurance exercise affected dystrophic limb, diaphragm, and cardiac function. Diaphragm specific tension was reduced by 60% ( P < 0.05) in mice that performed 1 yr of volitional wheel running compared with sedentary mdx mice. Dorsiflexor mass (extensor digitorum longus and tibialis anterior) and function (extensor digitorum longus) were not altered by endurance training. In mice that performed 1 yr of volitional wheel running, plantarflexor mass (soleus and gastrocnemius) was increased and soleus tetanic force was increased 36%, while specific tension was similar in wheel-running and sedentary groups. Cardiac mass was increased 15%, left ventricle chamber size was increased 20% (diastole) and 18% (systole), and stroke volume was increased twofold in wheel-running compared with sedentary mdx mice. These data suggest that the dystrophic heart may undergo positive exercise-induced remodeling and that limb muscle function is largely unaffected. Most importantly, however, as the diaphragm most closely recapitulates the human disease, these data raise the possibility of exercise-mediated injury in dystrophic skeletal muscle.

scholarly journals Truncated dystrophins reduce muscle stiffness in the extensor digitorum longus muscle of mdx mice

2013 ◽  
Vol 114 (4) ◽  
pp. 482-489 ◽  
Author(s):  
Chady H. Hakim ◽  
Dongsheng Duan
Keyword(s):  
Extensor Digitorum Longus ◽  
Muscle Stiffness ◽  
Extensor Digitorum ◽  
Clinical Feature ◽  
Mdx Mice ◽  
Wild Type ◽  
Dmd Gene ◽  
Edl Muscle ◽  
Muscle Wasting Disease ◽  
Dystrophin Protein

Muscle stiffness is a major clinical feature in Duchenne muscular dystrophy (DMD). DMD is the most common lethal inherited muscle-wasting disease in boys, and it is caused by the lack of the dystrophin protein. We recently showed that the extensor digitorum longus (EDL) muscle of mdx mice (a DMD mouse model) exhibits disease-associated muscle stiffness. Truncated micro- and mini-dystrophins are the leading candidates for DMD gene therapy. Unfortunately, it has never been clear whether these truncated genes can mitigate muscle stiffness. To address this question, we examined the passive properties of the EDL muscle in transgenic mdx mice that expressed a representative mini- or micro-gene (ΔH2-R15, ΔR2-15/ΔR18-23/ΔC, or ΔR4-23/ΔC). The passive properties were measured at the ages of 6 and 20 mo and compared with those of age-matched wild-type and mdx mice. Despite significant truncation of the gene, surprisingly, the elastic and viscous properties were completely restored to the wild-type level in every transgenic strain we examined. Our results demonstrated for the first time that truncated dystrophin genes may effectively treat muscle stiffness in DMD.

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