Exercise enhances the expression of brain-derived neurotrophic factor in the hippocampus accompanied by epigenetic alterations in senescence-accelerated mice prone 8

Neurosci Lett. 2019 Jul 27;706:176-181. doi: 10.1016/j.neulet.2019.05.031. Epub 2019 May 17.


Exercise increases the expression of brain-derived neurotrophic factor (BDNF) in the hippocampus and beneficially contributes to cognitive function and is accompanied by epigenetic changes. Specifically, the activity levels of histone acetyltransferases (HATs) and histone deacetylases (HDACs) regulate histone acetylation and modulate gene transcription. The objective of the present study was to assess the effect of an exercise regimen over a long period on the expression of BDNF, tropomyosin receptor kinase B (TrkB) and p75, and the activity of HATs and HDACs in the degenerative hippocampus. We used senescence-accelerated mice (SAM), and specifically, 3-month-old SAM resistant 1 (SAMR1) and SAM prone 8 (SAMP8) strains. Mice were distributed into four groups based on accelerated senescence and exercise status. Mice in the exercise groups exercised on a treadmill for 45 min a day, 3 days a week, for 6 months. Exercise significantly increased BDNF expression and decreased the expression of p75 in both SAMR1 and SAMP8. In addition, aging decreased HAT activity, whereas exercise decreased HDAC activity and increased the activity ratio of HAT to HDAC (HAT/HDAC). Therefore, the present study revealed that despite accelerated senescence, exercise up-regulated the expression of BDNF along with decreased the expression of p75, a receptor involved in apoptotic signaling. Furthermore, exercise increased HAT/HDAC, which might beneficially contribute to the transcriptional regulation for degenerative changes in the hippocampus.

Keywords: Aging; Epigenetics; Exercise; Hippocampus; Neurotrophin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aging / physiology*
  • Animals
  • Brain-Derived Neurotrophic Factor / metabolism*
  • Cognition / physiology
  • Epigenesis, Genetic / physiology*
  • Gene Expression Regulation
  • Hippocampus / metabolism*
  • Histone Acetyltransferases / metabolism
  • Histone Deacetylases / metabolism
  • Male
  • Membrane Glycoproteins / metabolism
  • Mice
  • Physical Conditioning, Animal / physiology*
  • Protein-Tyrosine Kinases / metabolism
  • Receptor, Nerve Growth Factor / metabolism


  • Brain-Derived Neurotrophic Factor
  • Membrane Glycoproteins
  • Receptor, Nerve Growth Factor
  • Histone Acetyltransferases
  • Ntrk2 protein, mouse
  • Protein-Tyrosine Kinases
  • Histone Deacetylases