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Pre- and postsynaptic changes in the neuromuscular junction in dystrophic mice

Duchenne muscular dystrophy (DMD) is a devastating neuromuscular disease in which weakness, increased susceptibility to muscle injury, and inadequate repair appear to underlie the pathology. While most attention has focused within the muscle fiber, we recently demonstrated in mdx mice (murine model...

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Autores principales: Pratt, Stephen J. P., Valencia, Ana P., Le, Gloribel K., Shah, Sameer B., Lovering, Richard M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4563167/
https://www.ncbi.nlm.nih.gov/pubmed/26441672
http://dx.doi.org/10.3389/fphys.2015.00252
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author Pratt, Stephen J. P.
Valencia, Ana P.
Le, Gloribel K.
Shah, Sameer B.
Lovering, Richard M.
author_facet Pratt, Stephen J. P.
Valencia, Ana P.
Le, Gloribel K.
Shah, Sameer B.
Lovering, Richard M.
author_sort Pratt, Stephen J. P.
collection PubMed
description Duchenne muscular dystrophy (DMD) is a devastating neuromuscular disease in which weakness, increased susceptibility to muscle injury, and inadequate repair appear to underlie the pathology. While most attention has focused within the muscle fiber, we recently demonstrated in mdx mice (murine model for DMD) significant morphologic alterations at the motor endplate of the neuromuscular junction (NMJ) and corresponding NMJ transmission failure after injury. Here we extend these initial observations at the motor endplate to gain insight into the pre- vs. postsynaptic morphology, as well as the subsynaptic nuclei in healthy (WT) vs. mdx mice. We quantified the discontinuity and branching of the terminal nerve in adult mice. We report mdx- and age-dependent changes for discontinuity and an increase in branching when compared to WT. To examine mdx- and age-dependent changes in the relative localization of pre- and postsynaptic structures, we calculated NMJ occupancy, defined as the ratio of the footprint occupied by presynaptic vesicles vs. that of the underlying motor endplate. The normally congruent coupling between presynaptic and postsynaptic morphology was altered in mdx mice, independent of age. Finally we found an almost two-fold increase in the number of nuclei and an increase in density (nuclei/area) underlying the NMJ. These outcomes suggest substantial remodeling of the NMJ during dystrophic progression. This remodeling reflects plasticity in both pre- and postsynaptic contributors to NMJ structure, and thus perhaps also NM transmission and muscle function.
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spelling pubmed-45631672015-10-05 Pre- and postsynaptic changes in the neuromuscular junction in dystrophic mice Pratt, Stephen J. P. Valencia, Ana P. Le, Gloribel K. Shah, Sameer B. Lovering, Richard M. Front Physiol Physiology Duchenne muscular dystrophy (DMD) is a devastating neuromuscular disease in which weakness, increased susceptibility to muscle injury, and inadequate repair appear to underlie the pathology. While most attention has focused within the muscle fiber, we recently demonstrated in mdx mice (murine model for DMD) significant morphologic alterations at the motor endplate of the neuromuscular junction (NMJ) and corresponding NMJ transmission failure after injury. Here we extend these initial observations at the motor endplate to gain insight into the pre- vs. postsynaptic morphology, as well as the subsynaptic nuclei in healthy (WT) vs. mdx mice. We quantified the discontinuity and branching of the terminal nerve in adult mice. We report mdx- and age-dependent changes for discontinuity and an increase in branching when compared to WT. To examine mdx- and age-dependent changes in the relative localization of pre- and postsynaptic structures, we calculated NMJ occupancy, defined as the ratio of the footprint occupied by presynaptic vesicles vs. that of the underlying motor endplate. The normally congruent coupling between presynaptic and postsynaptic morphology was altered in mdx mice, independent of age. Finally we found an almost two-fold increase in the number of nuclei and an increase in density (nuclei/area) underlying the NMJ. These outcomes suggest substantial remodeling of the NMJ during dystrophic progression. This remodeling reflects plasticity in both pre- and postsynaptic contributors to NMJ structure, and thus perhaps also NM transmission and muscle function. Frontiers Media S.A. 2015-09-09 /pmc/articles/PMC4563167/ /pubmed/26441672 http://dx.doi.org/10.3389/fphys.2015.00252 Text en Copyright © 2015 Pratt, Valencia, Le, Shah and Lovering. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Physiology
Pratt, Stephen J. P.
Valencia, Ana P.
Le, Gloribel K.
Shah, Sameer B.
Lovering, Richard M.
Pre- and postsynaptic changes in the neuromuscular junction in dystrophic mice
title Pre- and postsynaptic changes in the neuromuscular junction in dystrophic mice
title_full Pre- and postsynaptic changes in the neuromuscular junction in dystrophic mice
title_fullStr Pre- and postsynaptic changes in the neuromuscular junction in dystrophic mice
title_full_unstemmed Pre- and postsynaptic changes in the neuromuscular junction in dystrophic mice
title_short Pre- and postsynaptic changes in the neuromuscular junction in dystrophic mice
title_sort pre- and postsynaptic changes in the neuromuscular junction in dystrophic mice
topic Physiology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4563167/
https://www.ncbi.nlm.nih.gov/pubmed/26441672
http://dx.doi.org/10.3389/fphys.2015.00252
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