Format

Send to

Choose Destination
Proc Natl Acad Sci U S A. 2016 Jan 19;113(3):746-50. doi: 10.1073/pnas.1524272113. Epub 2016 Jan 5.

Sympathetic innervation controls homeostasis of neuromuscular junctions in health and disease.

Author information

1
Interdisciplinary Center for Neurosciences, Universität Heidelberg, 69120 Heidelberg, Germany; Institute of Molecular and Cell Biology, Hochschule Mannheim, 68163 Mannheim, Germany; Institute of Toxicology and Genetics, Karlsruhe Institute of Technology, 76344 Eggenstein-Leopoldshafen, Germany;
2
Department of Physiology, Faculdade de Medicina de Ribeirão Preto, University of São Paulo, 14049-900 Ribeirão Preto, Brazil; Department of Biochemistry and Immunology, Faculdade de Medicina de Ribeirão Preto, University of São Paulo, 14049-900 Ribeirão Preto, Brazil;
3
The John Walton Muscular Dystrophy Research Centre, Medical Research Council Centre for Neuromuscular Diseases, Newcastle University, Newcastle upon Tyne NE1 3BZ, United Kingdom;
4
Institute of Applied Informatics, Karlsruhe Institute of Technology, 76344 Eggenstein-Leopoldshafen, Germany;
5
Developmental Neurobiology Laboratory, European Neuroscience Institute, 37077 Göttingen, Germany;
6
Department of Integrative Pathophysiology, Universität Heidelberg, 68167 Mannheim, Germany;
7
Commissariat a l'energie atomique, Institut de Biologie et Technologies de Saclay (iBiTec-S), Service d'Ingénierie Moléculaire des Protéines (SIMOPRO), 91191 Gif-sur-Yvette Cedex, France; Institut des Neurosciences Paris-Saclay, UMR 9197, CNRS/Université Paris-Sud, 91190 Gif-sur-Yvette Cedex, France;
8
Max Planck Institute for Medical Research, 69120 Heidelberg, Germany;
9
Department of Biomedical Sciences, University of Padua, 35121 Padua, Italy; Institute of Neuroscience, Padua Section, National Research Council, 35121 Padua, Italy tullio.pozzan@unipd.it r.rudolf@hs-mannheim.de.
10
Interdisciplinary Center for Neurosciences, Universität Heidelberg, 69120 Heidelberg, Germany; Institute of Molecular and Cell Biology, Hochschule Mannheim, 68163 Mannheim, Germany; Institute of Toxicology and Genetics, Karlsruhe Institute of Technology, 76344 Eggenstein-Leopoldshafen, Germany; tullio.pozzan@unipd.it r.rudolf@hs-mannheim.de.

Abstract

The distribution and function of sympathetic innervation in skeletal muscle have largely remained elusive. Here we demonstrate that sympathetic neurons make close contact with neuromuscular junctions and form a network in skeletal muscle that may functionally couple different targets including blood vessels, motor neurons, and muscle fibers. Direct stimulation of sympathetic neurons led to activation of muscle postsynaptic β2-adrenoreceptor (ADRB2), cAMP production, and import of the transcriptional coactivator peroxisome proliferator-activated receptor γ-coactivator 1α (PPARGC1A) into myonuclei. Electrophysiological and morphological deficits of neuromuscular junctions upon sympathectomy and in myasthenic mice were rescued by sympathicomimetic treatment. In conclusion, this study identifies the neuromuscular junction as a target of the sympathetic nervous system and shows that sympathetic input is crucial for synapse maintenance and function.

KEYWORDS:

beta-agonists; cAMP; myasthenia; neuromuscular junction; sympathetic neurons

PMID:
26733679
PMCID:
PMC4725522
DOI:
10.1073/pnas.1524272113
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for HighWire Icon for PubMed Central
Loading ...
Support Center