title: Effects of in vivo injury on the neuromuscular junction in healthy and dystrophic muscles.
abstract: The most common and severe form of muscular dystrophy is Duchenne muscular dystrophy (DMD), a disorder caused by the absence of dystrophin, a structural protein found on the cytoplasmic surface of the sarcolemma of striated muscle fibres. Considerable attention has been dedicated to studying myofibre damage and muscle plasticity, but there is little information to determine if damage from contraction-induced injury occurs at or near the nerve terminal axon. We used α-bungarotoxin to compare neuromuscular junction (NMJ) morphology in healthy (wild-type, WT) and dystrophic (mdx) mouse quadriceps muscles and evaluated transcript levels of the post-synaptic muscle-specific kinase signalling complex. Our focus was to study changes in NMJs after injury induced with an established in vivo animal injury model. Neuromuscular transmission, electromyography (EMG), and NMJ morphology were assessed 24 h after injury. In non-injured muscle, muscle-specific kinase expression was significantly decreased in mdx compared to WT. Injury resulted in a significant loss of maximal torque in WT (39 ± 6%) and mdx (76 ± 8%) quadriceps, but significant changes in NMJ morphology, neuromuscular transmission and EMG data were found only in mdx following injury. Compared with WT mice, motor end-plates of mdx mice demonstrated less continuous morphology, more disperse acetylcholine receptor aggregates and increased number of individual acetylcholine receptor clusters, an effect that was exacerbated following injury. Neuromuscular transmission failure increased and the EMG measures decreased after injury in mdx mice only. The data show that eccentric contraction-induced injury causes morphological and functional changes to the NMJs in mdx skeletal muscle, which may play a role in excitation-contraction coupling failure and progression of the dystrophic process.
authors.affiliation: Department of Orthopaedics, University of Maryland School of Medicine, Baltimore, MD 21201, USA.
authors.forename: Stephen J P
authors.initials: SJP
authors.lastname: Pratt
authors.forename: Sameer B
authors.initials: SB
authors.lastname: Shah
authors.forename: Christopher W
authors.initials: CW
authors.lastname: Ward
authors.forename: Mario P
authors.initials: MP
authors.lastname: Inacio
authors.forename: Joseph P
authors.initials: JP
authors.lastname: Stains
authors.forename: Richard M
authors.initials: RM
authors.lastname: Lovering
mesh_terms: D000818:Animals; D001369:Axons / Q000648:ultrastructure; D002038:Bungarotoxins; D016189:Dystrophin / Q000235:genetics; D015870:Gene Expression; D007537:Isometric Contraction; D051379:Mice; D008810:Mice, Inbred C57BL; D009045:Motor Endplate / Q000166:cytology; D018482:Muscle, Skeletal / Q000503:physiopathology*; D020388:Muscular Dystrophy, Duchenne / Q000235:genetics / Q000473:pathology* / Q000503:physiopathology*; D009469:Neuromuscular Junction / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D012333:RNA, Messenger / Q000096:biosynthesis; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics / Q000378:metabolism; D011950:Receptors, Cholinergic / Q000378:metabolism; D019415:Torque
chemical_list: D002038:Bungarotoxins; D016189:Dystrophin; D012333:RNA, Messenger; D011950:Receptors, Cholinergic; C511695:MuSK protein, mouse; D020794:Receptor Protein-Tyrosine Kinases