Aerobic endurance capacity affects spatial memory and SIRT1 is a potent modulator of 8-oxoguanine repair

Neuroscience. 2013 Nov 12;252:326-36. doi: 10.1016/j.neuroscience.2013.08.020. Epub 2013 Aug 22.

Abstract

Regular exercise promotes brain function via a wide range of adaptive responses, including the increased expression of antioxidant and oxidative DNA damage-repairing systems. Accumulation of oxidized DNA base lesions and strand breaks is etiologically linked to for example aging processes and age-associated diseases. Here we tested whether exercise training has an impact on brain function, extent of neurogenesis, and expression of 8-oxoguanine DNA glycosylase-1 (Ogg1) and SIRT1 (silent mating-type information regulation 2 homolog). To do so, we utilized strains of rats with low- and high-running capacity (LCR and HCR) and examined learning and memory, DNA synthesis, expression, and post-translational modification of Ogg1 hippocampal cells. Our results showed that rats with higher aerobic/running capacity had better spatial memory, and expressed less Ogg1, when compared to LCR rats. Furthermore, exercise increased SIRT1 expression and decreased acetylated Ogg1 (AcOgg1) levels, a post-translational modification important for efficient repair of 8-oxo-7,8-dihydroguanine (8-oxoG). Our data on cell cultures revealed that nicotinamide, a SIRT1-specific inhibitor, caused the greatest increase in the acetylation of Ogg1, a finding further supported by our other observations that silencing SIRT1 also markedly increased the levels of AcOgg1. These findings imply that high-running capacity is associated with increased hippocampal function, and SIRT1 level/activity and inversely correlates with AcOgg1 levels and thereby the repair of genomic 8-oxoG.

Keywords: 4-dinitrophenylhydrazine; 5-bromo-2′-deoxyuridine; 8-oxo-7,8-dihydroguanine; 8-oxoG; 8-oxoguanine DNA glycosylase-1; AP; APE1; Ac; AcOgg1; BER; BrdU; DNA repair; DNPH; ERK; GAD; HCR; HDAC; HRP; LCR; NAD; NAM; NGF; OGG1; Ogg1; TBS; TBS-T; TSA; TrHCR; TrLCR; abasic; acetylated; acetylated 8-oxoguanine DNA glycosylase-1; apurinic apyrimidinic endonuclease1; base excision repair; exercise; extracellular signal-regulated kinase; glutamic acid decarboxylase; high-running capacity; hippocampus; histone deacetylase; horseradish peroxidase; low-running capacity; nerve growth factor; nicotinamide; nicotinamide adenine dinucleotide; single-strand breaks; ssbs; trained HCR; trained LCR; trichostatin A; tris-buffered saline; tris-buffered saline containing 0.1% Tween.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blotting, Western
  • DNA Glycosylases / biosynthesis*
  • DNA Repair / physiology
  • Gene Knockdown Techniques
  • Guanine / analogs & derivatives
  • Guanine / metabolism
  • Immunohistochemistry
  • Male
  • Memory / physiology*
  • Physical Conditioning, Animal / physiology*
  • Physical Endurance / physiology
  • RNA, Small Interfering
  • Rats
  • Real-Time Polymerase Chain Reaction
  • Sirtuin 1 / biosynthesis*
  • Spatial Behavior / physiology*

Substances

  • RNA, Small Interfering
  • 8-hydroxyguanine
  • Guanine
  • DNA Glycosylases
  • OGG1 protein, rat
  • Sirt1 protein, rat
  • Sirtuin 1