Sodium 4-phenylbutyrate reduces myofiber damage in a mouse model of Duchenne muscular dystrophy

Begam, Morium; Abro, Valerie M.; Mueller, Amber L.; Roche, Joseph A.

doi:10.1139/apnm-2016-0173

Cited by 10 publications

(12 citation statements)

References 17 publications

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“…On additional TA muscle sections prepared as above, we assessed sarcolemmal and myofiber damage, respectively, based on the presence of mouse immunoglobulin G (IgG(+)) and loss of desmin labeling (desmin(−)) in the myoplasm of myofibers, as described (Begam et al. ).…”

Section: Methodsmentioning

confidence: 99%

“…To evaluate the general morphology of the TA and quantify myofiber damage, we performed hematoxylin and eosin (H&E) staining on 5 lm cross sections as described (Roche et al , 2015Begam et al 2016). On additional TA muscle sections prepared as above, we assessed sarcolemmal and myofiber damage, respectively, based on the presence of mouse immunoglobulin G (IgG (+)) and loss of desmin labeling (desmin(À)) in the myoplasm of myofibers, as described (Begam et al 2016).…”

Section: Histological Studiesmentioning

confidence: 99%

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Diltiazem improves contractile properties of skeletal muscle in dysferlin-deficient BLAJ mice, but does not reduce contraction-induced muscle damage

et al. 2018

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B6.A‐Dysf prmd/GeneJ (BLAJ) mice model human limb‐girdle muscular dystrophy 2B (LGMD2B), which is linked to mutations in the dysferlin (DYSF) gene. We tested the hypothesis that, the calcium ion (Ca2+) channel blocker diltiazem (DTZ), reduces contraction‐induced skeletal muscle damage, in BLAJ mice. We randomly assigned mice (N = 12; 3–4 month old males) to one of two groups – DTZ (N = 6) or vehicle (VEH, distilled water, N = 6). We conditioned mice with either DTZ or VEH for 1 week, after which, their tibialis anterior (TA) muscles were tested for contractile torque and susceptibility to injury from forced eccentric contractions. We continued dosing with DTZ or VEH for 3 days following eccentric contractions, and then studied torque recovery and muscle damage. We analyzed contractile torque before eccentric contractions, immediately after eccentric contractions, and at 3 days after eccentric contractions; and counted damaged fibers in the injured and uninjured TA muscles. We found that DTZ improved contractile torque before and immediately after forced eccentric contractions, but did not reduce delayed‐onset muscle damage that was observed at 3 days after eccentric contractions.

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Section: Methodsmentioning

confidence: 99%

Section: Histological Studiesmentioning

confidence: 99%

Diltiazem improves contractile properties of skeletal muscle in dysferlin-deficient BLAJ mice, but does not reduce contraction-induced muscle damage

et al. 2018

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“…Since desmin is highly sensitive to muscle fiber damage, we colabeled QF sections with rabbit polyclonal primary antibodies to desmin (RB-9014-P, 1:200, ThermoFisher Scientific, Waltham, MA), to detect damaged fibers in the QF. 19 , 20 After overnight incubation and washing, as above; we incubated sections with secondary antibodies conjugated to Alexa 488 for 60 min (goat-anti-rabbit F(ab’)2 fragments, A-11070, 1:200, ThermoFisher Scientific).…”

Section: Methodsmentioning

confidence: 99%

“…On serial sections of the TA muscle, we labeled desmin and IgG, to detect damaged fibers, as described earlier and in Supplementary Methods. 20 , 22 As above, we incubated sections overnight with primary antibodies to desmin, washed the sections, and then applied goat anti-rabbit secondary antibodies. While applying goat anti-rabbitsecondary antibodies, we simultaneously applied goat anti-mouse IgG antibodies conjugated to biotin, in order to label mouse IgG.…”

Section: Methodsmentioning

confidence: 99%

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Damaged muscle fibers might masquerade as hybrid fibers – a cautionary note on immunophenotyping mouse muscle with mouse monoclonal antibodies

Begam¹,

Roche²

2018

Eur J Histochem

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We report that, labeling mouse muscle tissue, with mouse monoclonal antibodies specific to slow or fast myosin heavy chain (sMyHC and fMyHC, respectively), can lead to artefactual labeling of damaged muscle fibers, as hybrid fibers (sMyHC+ and fMyHC+). We demonstrate that, such erroneous immunophenotyping of muscle may be avoided, by performing colabeling or serialsection- labeling, to identify damaged fibers. The quadriceps femorismuscle group (QF) in 7-month-old, male, C57BL/6J mice had: 1.21±0.21%, 98.34±1.06%, 0.07±0.01%, and 0.53±0.85% fibers, that were, sMyHC+, fMyHC+, hybrid, and damaged, respectively. All fibers in the tibialis anterior muscle (TA) of 3-month-old, male, C57BL/6J mice were fMyHC+; and at 3 days after injurious eccentric contractions, there was no fiber-type shift, but ~ 18% fibers were damaged.

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The effects of concentric and eccentric training in murine models of dysferlin‐associated muscular dystrophy

et al. 2020

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IntroductionDysferlin‐deficient murine muscle sustains severe damage after repeated eccentric contractions.MethodsWith a robotic dynamometer, we studied the response of dysferlin‐sufficient and dysferlin‐deficient mice to 12 weeks of concentrically or eccentrically biased contractions. We also studied whether concentric contractions before or after eccentric contractions reduced muscle damage in dysferlin‐deficient mice.ResultsAfter 12 weeks of concentric training, there was no net gain in contractile force in dysferlin‐sufficient or dysferlin‐deficient mice, whereas eccentric training produced a net gain in force in both mouse strains. However, eccentric training induced more muscle damage in dysferlin‐deficient vs dysferlin‐sufficient mice. Although concentric training produced minimal muscle damage in dysferlin‐deficient mice, it still led to a prominent increase in centrally nucleated fibers. Previous exposure to concentric contractions conferred slight protection on dysferlin‐deficient muscle against damage from subsequent injurious eccentric contractions.DiscussionConcentric contractions may help dysferlin‐deficient muscle derive the benefits of exercise without inducing damage.

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Sodium 4-phenylbutyrate reduces myofiber damage in a mouse model of Duchenne muscular dystrophy

Cited by 10 publications

References 17 publications

Diltiazem improves contractile properties of skeletal muscle in dysferlin-deficient BLAJ mice, but does not reduce contraction-induced muscle damage

Diltiazem improves contractile properties of skeletal muscle in dysferlin-deficient BLAJ mice, but does not reduce contraction-induced muscle damage

Damaged muscle fibers might masquerade as hybrid fibers – a cautionary note on immunophenotyping mouse muscle with mouse monoclonal antibodies

The effects of concentric and eccentric training in murine models of dysferlin‐associated muscular dystrophy

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