The Effect of 4 Weeks of Aerobic Training on Cognitive Function and Expression Level of PGC1α and VEGF Genes in the Hippocampus of Rats with Alzheimer’s Disease

Abstract

Background & objective: Alzheimer's disease (AD) is the most common cause of dementia among the elderly, threatening their quality of life. On the other hand, regular exercise is associated with improved brain health and cognitive function. However, the mechanisms of these benefits have not yet been fully elucidated. Therefore, the aim of this study was to investigate the effect of 4 weeks of moderate intensity interval aerobic training on cognitive function and expression level of PGC1α and VEGF genes in the hippocampus of old rats with AD. Methods: For this purpose, 20-month-old male Wistar rats were divided into three groups of AD (n=8), AD+exercise training (n=8) and control (n=8). Intra-hippocampal injection of Aβ 42 was used to induce AD. The animals in the exercise group performed moderate-intensity interval aerobic exercise for 4 weeks, 5 days a week. To assess spatial learning and memory, the animals underwent the Morris water maze test 48 hours following the last training session. Then, the animals were killed and hippocampal tissue was extracted. Real time-PCR method was used to measure gene expression. Statistical analysis was performed using one-way analysis of variance and Pearson correlation coefficient at the significance level of p  0.05. Results: The results showed that Aβ 42 injection impaired spatial learning and memory function and reduced the expression level of PGC1α and VEGF genes in hippocampal tissue ( p  0.05). Aerobic exercise improved spatial learning and memory function and increased PGC1α and VEGF genes expression ( p  0.01). Also, a significant positive relationship was observed between the PGC1α and VEGF gene expression levels in the hippocampus (r= 0.859, p ≤0.01). In addition, there was a significant inverse relationship between PGC1α and VEGF genes expression and the mean time spent to find the platform (r= -0.9, p  0.01 and r= -0.750, p  0.01, respectively), and a significant positive relationship with the time spent in the target quadrant (r= -0.794, p  0.01 and r= -0.632, p  0.01, respectively). Conclusion: In general, aerobic training improves spatial learning and memory performance in old animals with AD; up-regulation of the exercise-induced PGC1α/VEGF pathway in the brain, at least in part, appears to be involved in this adaptation.