Sympathetic innervation controls homeostasis of neuromuscular junctions in health and disease

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


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Active Transport, Cell Nucleus
  • Animals
  • Biosensing Techniques
  • Cell Nucleus / metabolism
  • Cyclic AMP / metabolism
  • Female
  • Health*
  • Homeostasis*
  • Male
  • Mice, Inbred C57BL
  • Models, Biological
  • Muscle, Skeletal / innervation
  • Nervous System Diseases / pathology*
  • Neuromuscular Junction / metabolism
  • Neuromuscular Junction / pathology*
  • Neurons / metabolism
  • Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha
  • Phenotype
  • Signal Transduction
  • Sympathectomy
  • Sympathetic Nervous System / metabolism
  • Sympathetic Nervous System / pathology*
  • Transcription Factors / metabolism


  • Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha
  • Ppargc1a protein, mouse
  • Transcription Factors
  • Cyclic AMP