Abstract:
During advancing age, reduction of microvessels in the brain contributes insufficiency tissue perfusion. Mounting evidence indicates that microvascular deterioration in aged brain relates to oxidative stress. Nuclear factor erythroid-related factor 2 (Nrf2) plays an important role in cellular antioxidant defense. Regular physical exercise is well known to have beneficial effect to brain health, including promoted blood flow and augmented angiogenesis, in aging individuals. However, the underlying mechanism of regular physical exercise in improvement of brain microvascular density during advancing age has not been fully elucidated. This study aimed to investigate the underlying mechanism of exercise training in improvement of microvascular density associated with PI3K/Akt/Nrf2 pathway in aged rat brain. Male Wistar rats were divided into three groups; sedentary-young (SY), sedentary-age (SA) and trained-age (TA). Exercise program included swimming exercise for eight weeks. Expression of CD31 (as indicator of microvascular density) and Nrf2 were evaluated by immunohistochemistry staining. Activity of Nrf2, protein levels of phosphatidylinositol-4,5-biphosphate 3-kinase (PI3K) and phosphorylated-protein kinase B (p-Akt) in isolated brain microvessels were assessed by immunoassay. Aging (SA) induced significant reduction of brain microvascular density and expression of Nrf2, PI3K and p-Akt proteins, as well as Nrf2 activity, comparing to those of SY group. The eight-week exercise training significantly improved brain microvascular density and upregulated Nrf2, PI3K and p-Akt proteins as well as activated Nrf2 activity, than that of the age group without exercise (SA). In conclusion, exercise training can improve brain microvascular deterioration associated with PI3K/Akt/Nrf2 pathway in aging rats.
