Running and Swimming Differently Adapt the BDNF/TrkB Pathway to a Slow Molecular Pattern at the NMJ

Int J Mol Sci. 2021 Apr 27;22(9):4577. doi: 10.3390/ijms22094577.


Physical exercise improves motor control and related cognitive abilities and reinforces neuroprotective mechanisms in the nervous system. As peripheral nerves interact with skeletal muscles at the neuromuscular junction, modifications of this bidirectional communication by physical activity are positive to preserve this synapse as it increases quantal content and resistance to fatigue, acetylcholine receptors expansion, and myocytes' fast-to-slow functional transition. Here, we provide the intermediate step between physical activity and functional and morphological changes by analyzing the molecular adaptations in the skeletal muscle of the full BDNF/TrkB downstream signaling pathway, directly involved in acetylcholine release and synapse maintenance. After 45 days of training at different intensities, the BDNF/TrkB molecular phenotype of trained muscles from male B6SJLF1/J mice undergo a fast-to-slow transition without affecting motor neuron size. We provide further knowledge to understand how exercise induces muscle molecular adaptations towards a slower phenotype, resistant to prolonged trains of stimulation or activity that can be useful as therapeutic tools.

Keywords: BDNF/TrkB signaling; endurance exercise; neuromuscular junction; new activity conditions; skeletal muscle.

MeSH terms

  • Animals
  • Brain-Derived Neurotrophic Factor / metabolism*
  • Male
  • Membrane Glycoproteins / metabolism*
  • Mice, Inbred Strains
  • Motor Neurons / metabolism
  • Munc18 Proteins / metabolism
  • Muscle, Skeletal / physiology
  • Nerve Growth Factors / metabolism
  • Neuromuscular Junction / metabolism*
  • Physical Conditioning, Animal / physiology
  • Protein Serine-Threonine Kinases / metabolism
  • Protein-Tyrosine Kinases / metabolism*
  • Running / physiology*
  • Signal Transduction
  • Swimming / physiology*
  • Synaptic Vesicles / metabolism
  • Synaptosomal-Associated Protein 25 / metabolism


  • Bdnf protein, mouse
  • Brain-Derived Neurotrophic Factor
  • Membrane Glycoproteins
  • Munc18 Proteins
  • Nerve Growth Factors
  • SNAP25 protein, human
  • Stxbp1 protein, mouse
  • Synaptosomal-Associated Protein 25
  • Ntrk2 protein, mouse
  • Protein-Tyrosine Kinases
  • Protein Serine-Threonine Kinases