AEROBIC ENDURANCE CAPACITY AFFECTS SPATIAL MEMORY AND SIRT1 IS A POTENT MODULATOR OF 8-OXOGUANINE REPAIR

作者：Sarga, L.; Hart, N.; Koch, L. G.; Britton, S. L.; Hajas, G.; Boldogh, I.; Ba, X.; Radak, Z.^*

来源：Neuroscience, 2013, 252: 326-336.

DOI：10.1016/j.neuroscience.2013.08.020

• DNA repair
• OGG1
• exercise
• hippocampus

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.

• 出版日期2013-11-12
• 单位东北师范大学