Circulating insulin-like growth factor I mediates effects of exercise on the brain

J Neurosci. 2000 Apr 15;20(8):2926-33. doi: 10.1523/JNEUROSCI.20-08-02926.2000.


Physical exercise increases brain activity through mechanisms not yet known. We now report that in rats, running induces uptake of blood insulin-like growth factor I (IGF-I) by specific groups of neurons throughout the brain. Neurons accumulating IGF-I show increased spontaneous firing and a protracted increase in sensitivity to afferent stimulation. Furthermore, systemic injection of IGF-I mimicked the effects of exercise in the brain. Thus, brain uptake of IGF-I after either intracarotid injection or after exercise elicited the same pattern of neuronal accumulation of IGF-I, an identical widespread increase in neuronal c-Fos, and a similar stimulation of hippocampal brain-derived neurotrophic factor. When uptake of IGF-I by brain cells was blocked, the exercise-induced increase on c-Fos expression was also blocked. We conclude that serum IGF-I mediates activational effects of exercise in the brain. Thus, stimulation of the uptake of blood-borne IGF-I by nerve cells may lead to novel neuroprotective strategies.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Action Potentials / drug effects
  • Action Potentials / physiology
  • Animals
  • Brain / drug effects
  • Brain / metabolism*
  • Choroid Plexus / metabolism*
  • Female
  • Humans
  • Insulin-Like Growth Factor I / cerebrospinal fluid
  • Insulin-Like Growth Factor I / pharmacokinetics*
  • Male
  • Physical Conditioning, Animal / physiology*
  • Proto-Oncogene Proteins c-fos / metabolism*
  • Purkinje Cells / metabolism*
  • Rats
  • Rats, Wistar


  • Proto-Oncogene Proteins c-fos
  • Insulin-Like Growth Factor I