摘要 : Oxidative damage and mitochondrial dysfunction are two prominent pathological features and gradually understood as important pathogenic events for neurodegenerative diseases, including aging and Alzheimer's disease (AD). The prese... 展开 Oxidative damage and mitochondrial dysfunction are two prominent pathological features and gradually understood as important pathogenic events for neurodegenerative diseases, including aging and Alzheimer's disease (AD). The present study was aimed to explore the prolonged treatment of pramipexole (PPX) following amyloid beta (A beta(1-42))-induced cognitive impairments , oxidative stress, and mitochondrial dysfunction in a Wistar rat model. We have found that PPX (1.0 mg/kg, b.wt.) improves cognitive impairments of A beta(1-42)-infused rats in Morris water maze. At the same time, PPX attenuated A beta(1-42)-induced oxidative damage and increased reduced-glutathione content level, decreased lipid peroxidation rate and suppressed the activity of acetylcholinesterase and shows antioxidant effects. Additionally, PPX treatment has shown inhibition of mitochondrial reactive oxygen species production and restored mitochondrial membrane potential, oxidative phosphorylation, and enhanced ATP levels in A beta(1-42) rats. Furthermore, PPX treatment reduced bioenergetics loss and dynamics alterations by upregulating PGC-1 alpha protein level and mitigating translocation of Box and Drp-1 to mitochondria and cytochrome-c release into the cytoplasm. PPX also increased mitofusin-2 protein expression, a basic element of mitochondrial fusion process. We conclude that remedial role of PPX in mitigating oxidative damage and mitochondrial perturbation that are modulated in A beta(1-42) rats may have the propensity in AD pathogenesis. 收起