The role of pre-pubertal training history on hippocampal neurotrophic factors and glucocorticoid receptor protein levels in adult male rats

Neurosci Lett. 2021 May 1:752:135834. doi: 10.1016/j.neulet.2021.135834. Epub 2021 Mar 23.


Neurotrophic factors play an integral role in hippocampal plasticity, and interaction with HPA axis components, especially glucocorticoid receptors (GR), can mediate the structural and functional changes. In the present work, we investigated the long-term effects of combined exercise training (CET) and voluntary physical activity in an enriched environment (EE) in the pre-pubertal period on hippocampal neurotrophic factors and GR. For this purpose, a longitudinal study was designed. After three weeks, all rats were kept in the standard cages without any interventions until adulthood. Western blot analysis revealed a significant increase in hippocampal BDNF and VEGF protein levels in both EE and CET groups (P < 0.001), along with an increase in GR protein levels. In addition, EE decreased serum corticosterone levels compared to CET (P < 0.05). Serum insulin-like growth factor-1 (IGF-1) levels did not demonstrate remarkable changes between groups. Training interventions during sensitive developmental periods may produce profound and long-lasting effects on the hippocampus, at least in part by interactive effects of neurotrophic factors cascades and GR.

Keywords: Brain development; Enriched environment; Forced training; Glucocorticoid receptor; Neurotrophic factors.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adolescent Development / physiology*
  • Animals
  • Brain-Derived Neurotrophic Factor / analysis
  • Brain-Derived Neurotrophic Factor / metabolism
  • Hippocampus / growth & development*
  • Hippocampus / metabolism
  • Humans
  • Hypothalamo-Hypophyseal System / metabolism
  • Longitudinal Studies
  • Male
  • Models, Animal
  • Physical Conditioning, Animal / physiology*
  • Pituitary-Adrenal System / metabolism
  • Rats
  • Receptors, Glucocorticoid / analysis
  • Receptors, Glucocorticoid / metabolism
  • Vascular Endothelial Growth Factor A / analysis
  • Vascular Endothelial Growth Factor A / metabolism


  • Bdnf protein, rat
  • Brain-Derived Neurotrophic Factor
  • Receptors, Glucocorticoid
  • Vascular Endothelial Growth Factor A
  • vascular endothelial growth factor A, rat