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Recovery of altered neuromuscular junction morphology and muscle function in mdx mice after injury.
- Source :
-
Cellular and molecular life sciences : CMLS [Cell Mol Life Sci] 2015 Jan; Vol. 72 (1), pp. 153-64. Date of Electronic Publication: 2014 Jun 20. - Publication Year :
- 2015
-
Abstract
- Duchenne muscular dystrophy (DMD) is a devastating neuromuscular disease in which weakness, increased susceptibility to muscle injury, and inadequate repair underlie the pathology. While most attention has focused within the muscle fiber, we recently demonstrated significant alterations in the neuromuscular junction (NMJ) morphology and resulting neuromuscular transmission failure (NTF) 24 h after injury in mdx mice (murine model for DMD). Here we determine the contribution of NMJ morphology and NTF to the recovery of muscle contractile function post-injury. NMJ morphology and NTF rates were assessed day 0 (immediately after injury) and days 1, 7, 14 and 21 after quadriceps injury. Eccentric injury of the quadriceps resulted in a significant loss of maximal torque in both WT (39 ± 6 %) and mdx (76 ± 8 %) with a full recovery in WT by day 7 and in mdx by day 21. Post-injury alterations in NMJ morphology and NTF were found only in mdx, were limited to days 0 and 1, and were independent of changes in MuSK or AChR expression. Such early changes at the NMJ after injury are consistent with mechanical disruption rather than newly forming NMJs. Furthermore, we show that the dense microtubule network that underlies the NMJ is significantly reduced and disorganized in mdx compared to WT. These structural changes at the NMJ may play a role in the increased NMJ disruption and the exaggerated loss of nerve-evoked muscle force seen after injury to dystrophic muscles.
- Subjects :
- Animals
Blotting, Western
Cells, Cultured
Fluorescent Antibody Technique
Immunoprecipitation
Male
Mice
Mice, Inbred C57BL
Mice, Inbred mdx
Muscle Contraction
Muscular Dystrophy, Duchenne genetics
Muscular Dystrophy, Duchenne metabolism
Neuromuscular Junction physiopathology
RNA, Messenger genetics
Real-Time Polymerase Chain Reaction
Receptors, Cholinergic metabolism
Reverse Transcriptase Polymerase Chain Reaction
Dystrophin physiology
Muscular Dystrophy, Duchenne pathology
Neuromuscular Junction injuries
Neuromuscular Junction metabolism
Regeneration physiology
Subjects
Details
- Language :
- English
- ISSN :
- 1420-9071
- Volume :
- 72
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Cellular and molecular life sciences : CMLS
- Publication Type :
- Academic Journal
- Accession number :
- 24947322
- Full Text :
- https://doi.org/10.1007/s00018-014-1663-7