12
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: not found

      Morphological and functional remodeling of the neuromuscular junction by skeletal muscle PGC-1α

      research-article

      Read this article at

      ScienceOpenPublisherPMC
      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          The neuromuscular junction (NMJ) exhibits high morphological and functional plasticity. In the mature muscle, the relative levels of physical activity are major determinants of NMJ function. Classically, motor neuron-mediated activation patterns of skeletal muscle have been thought of as the major drivers of NMJ plasticity and the ensuing fiber-type determination in muscle. Here we use muscle-specific transgenic animals for the peroxisome proliferator-activated receptor γ co-activator 1α (PGC-1α) as a genetic model for trained mice to elucidate the contribution of skeletal muscle to activity-induced adaptation of the NMJ. We find that muscle-specific expression of PGC-1α promotes a remodeling of the NMJ, even in the absence of increased physical activity. Importantly, these plastic changes are not restricted to post-synaptic structures, but extended to modulation of pre-synaptic cell morphology and function. Therefore, our data indicate that skeletal muscle significantly contributes to the adaptation of the NMJ subsequent to physical activity.

          Related collections

          Most cited references39

          • Record: found
          • Abstract: found
          • Article: not found

          The role of exercise and PGC1alpha in inflammation and chronic disease.

          Inadequate physical activity is linked to many chronic diseases. But the mechanisms that tie muscle activity to health are unclear. The transcriptional coactivator PGC1alpha has recently been shown to regulate several exercise-associated aspects of muscle function. We propose that this protein controls muscle plasticity, suppresses a broad inflammatory response and mediates the beneficial effects of exercise.
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            Development of the vertebrate neuromuscular junction.

            We describe the formation, maturation, elimination, maintenance, and regeneration of vertebrate neuromuscular junctions (NMJs), the best studied of all synapses. The NMJ forms in a series of steps that involve the exchange of signals among its three cellular components--nerve terminal, muscle fiber, and Schwann cell. Although essentially any motor axon can form NMJs with any muscle fiber, an additional set of cues biases synapse formation in favor of appropriate partners. The NMJ is functional at birth but undergoes numerous alterations postnatally. One step in maturation is the elimination of excess inputs, a competitive process in which the muscle is an intermediary. Once elimination is complete, the NMJ is maintained stably in a dynamic equilibrium that can be perturbed to initiate remodeling. NMJs regenerate following damage to nerve or muscle, but this process differs in fundamental ways from embryonic synaptogenesis. Finally, we consider the extent to which the NMJ is a suitable model for development of neuron-neuron synapses.
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              Attenuation of age-related changes in mouse neuromuscular synapses by caloric restriction and exercise.

              The cellular basis of age-related behavioral decline remains obscure but alterations in synapses are likely candidates. Accordingly, the beneficial effects on neural function of caloric restriction and exercise, which are among the most effective anti-aging treatments known, might also be mediated by synapses. As a starting point in testing these ideas, we studied the skeletal neuromuscular junction (NMJ), a large, accessible peripheral synapse. Comparison of NMJs in young adult and aged mice revealed a variety of age-related structural alterations, including axonal swellings, sprouting, synaptic detachment, partial or complete withdrawal of axons from some postsynaptic sites, and fragmentation of the postsynaptic specialization. Alterations were significant by 18 mo of age and severe by 24 mo. A life-long calorie-restricted diet significantly decreased the incidence of pre- and postsynaptic abnormalities in 24-mo-old mice and attenuated age-related loss of motor neurons and turnover of muscle fibers. One month of exercise (wheel running) in 22-mo-old mice also reduced age-related synaptic changes but had no effect on motor neuron number or muscle fiber turnover. Time-lapse imaging in vivo revealed that exercise partially reversed synaptic alterations that had already occurred. These results demonstrate a critical effect of aging on synaptic structure and provide evidence that interventions capable of extending health span and lifespan can partially reverse these age-related synaptic changes.
                Bookmark

                Author and article information

                Journal
                101528555
                37539
                Nat Commun
                Nat Commun
                Nature communications
                2041-1723
                27 March 2014
                01 April 2014
                2014
                26 April 2016
                : 5
                : 3569
                Affiliations
                [1 ]Biozentrum, Div. of Pharmacology/Neurobiology, University of Basel, Klingelbergstrasse 50/70, CH-4056 Basel, Switzerland
                [2 ]Department of Medical Physiology and Biophysics, School of Medicine University of Seville, Avda. Sánchez Pizjuan 4, 41009 Sevilla, Spain
                [3 ]Department of Biochemistry, Rosalind and Morris Goodman Cancer Centre, McGill University, 3655 promenade Sir William Osler, Montreal, QC H3G 1Y6, Canada
                Author notes
                Correspondence to: Christoph Handschin ( christoph.handschin@ 123456unibas.ch )
                [#]

                deceased

                Article
                CAMS4221
                10.1038/ncomms4569
                4846352
                24686533
                23e1cb8e-60bc-4a93-9be2-9114accf13ee

                Users may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use: http://www.nature.com/authors/editorial_policies/license.html#terms

                History
                Categories
                Article

                Uncategorized
                neuromuscular junction,skeletal muscle,pgc-1α,electrophysiology,exercise,mitochondria,synaptic vesicles,synaptic folds

                Comments

                Comment on this article