Research Institute of Sport Science, Faculty of Physical Education and Sport Science, Semmelweis University, Budapest H-1123, Hungary; Department of Microbiology and Immunology, Sealy Center for Molecular Medicine, University of Texas Medical Branch at Galveston, Galveston, TX 77555, USA.
Neuroscience. 2013 Nov 12;252:326-36. doi: 10.1016/j.neuroscience.2013.08.020. Epub 2013 Aug 22.
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.
定期锻炼通过广泛的适应性反应促进大脑功能，包括增加抗氧化和氧化 DNA 损伤修复系统的表达。氧化 DNA 碱基损伤和链断裂的积累与例如衰老过程和与年龄相关的疾病有关。在这里，我们测试了运动训练是否对大脑功能、神经发生程度以及 8-氧鸟嘌呤 DNA 糖基化酶-1（Ogg1）和 SIRT1（沉默交配型信息调节 2 同源物）的表达有影响。为此，我们利用低跑和高跑能力的大鼠品系（LCR 和 HCR），并检查了学习和记忆、DNA 合成、Ogg1 海马细胞的表达和翻译后修饰。我们的结果表明，与 LCR 大鼠相比，具有更高有氧/跑步能力的大鼠具有更好的空间记忆，并且表达的 Ogg1 较少。此外，运动增加了 SIRT1 的表达并降低了乙酰化 Ogg1（AcOgg1）的水平，这是一种对有效修复 8-氧-7,8-二氢鸟嘌呤（8-oxoG）很重要的翻译后修饰。我们关于细胞培养的研究结果表明，烟酰胺，一种 SIRT1 特异性抑制剂，导致 Ogg1 的乙酰化程度最大增加，这一发现进一步得到了我们的其他观察结果的支持，即沉默 SIRT1 也显著增加了 AcOgg1 的水平。这些发现表明，高跑能力与海马功能的增强有关，而 SIRT1 水平/活性与 AcOgg1 水平呈负相关，从而修复基因组 8-oxoG。
