Effect of prolonged voluntary wheel running on oxidative stress and defence mechanisms in cortex and hippocampus of healthy female rats.

Physical exercise promotes brain health and cognitive function possibly through mechanisms that include strengthened resistance to oxidative stress. However, limited research has explored the cumulative effects of regular voluntary exercise on both oxidative stress and defence mechanisms in hippocampus and cortex, two regions essential for cognitive function. Especially, adaptations in the young, healthy brain are insufficiently understood. This study investigates the impact of 8 weeks of voluntary wheel running on oxidative damage and counteracting defence mechanisms in the cortex and hippocampus of young, healthy female rats. To this end, we assessed oxidative damage to proteins and DNA, antioxidant defence, and DNA repair mechanisms, focusing on the base excision repair pathway. Our findings show that 8 weeks of voluntary exercise does not significantly modify oxidative damage or antioxidant defences in either cortical or hippocampal brain regions. Instead, the voluntary wheel running intervention led to a reduction in the levels of DNA polymerase β and mitochondrial apurinic/apyrimidinic endonuclease 1, key enzymes involved in base excision repair. Moreover, mitochondrial DNA copy number increased in the cortex, but decreased in the hippocampus, suggesting distinct regional adaptations. Collectively, these results indicate that the healthy young brain maintains redox homeostasis despite reduced DNA repair capacity. By analysing a comprehensive array of biomarkers in two brain regions, this study addresses gaps in our current knowledge on prolonged training and brain health and provides valuable insights into how regular exercise produces region-specific and shared responses in the healthy state.