Running exercise- and antidepressant-induced increases in growth and survival-associated signaling molecules are IGF-dependent

Growth Factors. 2007 Apr;25(2):118-31. doi: 10.1080/08977190701602329.


It is known that physical exercise increases hippocampal brain-derived neurotrophic factor (BDNF) mRNA and protein, as well as the expression of several pro-survival signaling proteins and that many of these effects depend on the uptake of peripheral insulin-like growth factor-1 (IGF-1) into the CNS. Because treatment with antidepressants has similar effects upon neurotrophin expression, we investigated whether antidepressant-induced BDNF changes also depend on IGF-1 uptake, as well as whether IGF-1 plays a role in the exercise/antidepressant-induced expression of molecules associated with plasticity/growth (GAP-43, SCG-10) and the intracellular activation of molecules associated with neuronal survival (Akt, ERK1/2). We evaluated the effects of a well known monoamine oxidase inhibitor, tranylcypromine, on BDNF mRNA and protein levels and phospho-Akt and phospho-ERK1/2 immunoreactivity, both with and without systemic blockade of IGF-1 uptake through the use of an antiserum raised against IGF-1. Anti-IGF-1 reversed the increase in BDNF mRNA and protein elicited by exercise as well as tranylcypromine. Exercise also significantly enhanced transcription of axon growth protein, GAP-43, an effect that was also evidenced to be IGF-1-dependent. The combination of exercise-plus-tranylcypromine also increased several cell survival signaling measures, but the BDNF changes associated with the combination treatment appeared to be independent of IGF-1 uptake. Together, these results indicate that the uptake of peripheral IGF-1 in the CNS is essential for antidepressant- as well as exercise-induced enhancement in hippocampal BDNF expression and thus, enhanced hippocampal neuronal survival and plasticity.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Antidepressive Agents / therapeutic use*
  • Brain-Derived Neurotrophic Factor / metabolism*
  • Cell Proliferation
  • Hippocampus / metabolism
  • In Situ Hybridization
  • Male
  • Models, Biological
  • Monoamine Oxidase Inhibitors / pharmacology
  • Neurons / metabolism
  • Physical Conditioning, Animal*
  • RNA, Messenger / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Running
  • Signal Transduction
  • Somatomedins / metabolism*
  • Tranylcypromine / pharmacology


  • Antidepressive Agents
  • Brain-Derived Neurotrophic Factor
  • Monoamine Oxidase Inhibitors
  • RNA, Messenger
  • Somatomedins
  • Tranylcypromine