Physical activity and muscle-brain crosstalk

Nat Rev Endocrinol. 2019 Jul;15(7):383-392. doi: 10.1038/s41574-019-0174-x.


Neurological and mental illnesses account for a considerable proportion of the global burden of disease. Exercise has many beneficial effects on brain health, contributing to decreased risks of dementia, depression and stress, and it has a role in restoring and maintaining cognitive function and metabolic control. The fact that exercise is sensed by the brain suggests that muscle-induced peripheral factors enable direct crosstalk between muscle and brain function. Muscle secretes myokines that contribute to the regulation of hippocampal function. Evidence is accumulating that the myokine cathepsin B passes through the blood-brain barrier to enhance brain-derived neurotrophic factor production and hence neurogenesis, memory and learning. Exercise increases neuronal gene expression of FNDC5 (which encodes the PGC1α-dependent myokine FNDC5), which can likewise contribute to increased brain-derived neurotrophic factor levels. Serum levels of the prototype myokine, IL-6, increase with exercise and might contribute to the suppression of central mechanisms of feeding. Exercise also increases the PGC1α-dependent muscular expression of kynurenine aminotransferase enzymes, which induces a beneficial shift in the balance between the neurotoxic kynurenine and the neuroprotective kynurenic acid, thereby reducing depression-like symptoms. Myokine signalling, other muscular factors and exercise-induced hepatokines and adipokines are implicated in mediating the exercise-induced beneficial impact on neurogenesis, cognitive function, appetite and metabolism, thus supporting the existence of a muscle-brain endocrine loop.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Adipokines / metabolism
  • Animals
  • Biomarkers / metabolism
  • Brain / metabolism*
  • Brain-Derived Neurotrophic Factor / metabolism*
  • Exercise / physiology*
  • Female
  • Fibronectins / metabolism*
  • Humans
  • Male
  • Mice
  • Muscle, Skeletal / metabolism*
  • Rats
  • Signal Transduction
  • Sympathetic Nervous System


  • Adipokines
  • Biomarkers
  • Brain-Derived Neurotrophic Factor
  • FNDC5 protein, human
  • Fibronectins