title: Morphological and functional remodelling of the neuromuscular junction by skeletal muscle PGC-1α.
abstract: The neuromuscular junction (NMJ) exhibits high morphological and functional plasticity. In the mature muscle, the relative levels of physical activity are the 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 fibre-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 remodelling 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 presynaptic cell morphology and function. Therefore, our data indicate that skeletal muscle significantly contributes to the adaptation of the NMJ subsequent to physical activity.
authors.affiliation: Biozentrum, Division of Pharmacology/Neurobiology, University of Basel, Klingelbergstrasse 50/70, CH-4056 Basel, Switzerland.
authors.forename: Anne-Sophie
authors.initials: AS
authors.lastname: Arnold
authors.affiliation: Biozentrum, Division of Pharmacology/Neurobiology, University of Basel, Klingelbergstrasse 50/70, CH-4056 Basel, Switzerland.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Gill
authors.affiliation: 1] Biozentrum, Division of Pharmacology/Neurobiology, University of Basel, Klingelbergstrasse 50/70, CH-4056 Basel, Switzerland [2].
authors.forename: Martine
authors.initials: M
authors.lastname: Christe
authors.affiliation: Department of Medical Physiology and Biophysics, School of Medicine University of Seville, Avda. Sánchez Pizjuan 4, 41009 Sevilla, Spain.
authors.forename: Rocío
authors.initials: R
authors.lastname: Ruiz
authors.affiliation: Department of Biochemistry, Rosalind and Morris Goodman Cancer Centre, McGill University, 3655 promenade Sir William Osler, Montreal, Quebec, Canada H3G 1Y6.
authors.forename: Shawn
authors.initials: S
authors.lastname: McGuirk
authors.affiliation: Department of Biochemistry, Rosalind and Morris Goodman Cancer Centre, McGill University, 3655 promenade Sir William Osler, Montreal, Quebec, Canada H3G 1Y6.
authors.forename: Julie
authors.initials: J
authors.lastname: St-Pierre
authors.affiliation: Department of Medical Physiology and Biophysics, School of Medicine University of Seville, Avda. Sánchez Pizjuan 4, 41009 Sevilla, Spain.
authors.forename: Lucía
authors.initials: L
authors.lastname: Tabares
authors.affiliation: Biozentrum, Division of Pharmacology/Neurobiology, University of Basel, Klingelbergstrasse 50/70, CH-4056 Basel, Switzerland.
authors.forename: Christoph
authors.initials: C
authors.lastname: Handschin
mesh_terms: D000222:Adaptation, Physiological; D000818:Animals; D051379:Mice; D008822:Mice, Transgenic; D009119:Muscle Contraction; D018482:Muscle, Skeletal / Q000033:anatomy & histology / Q000378:metabolism*; D009469:Neuromuscular Junction / Q000033:anatomy & histology / Q000502:physiology*; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*
chemical_list: D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; C485290:Ppargc1a protein, mouse; D014157:Transcription Factors