摘要：Uric acid is a powerful antioxidant. However, its elevated levels in association with cardiovascular diseases predispose individuals to cognitive impairment. Uric acid’s effects on cognition may be related to its concentration and exposure period. We aimed to explore the effects of long-term elevated serum uric acid on cognitive function and hippocampus. Rats were randomly divided into four groups: NC, M1, M2 and M3 groups. Hyperuricemia was established in rats at week 6 and maintained until week 48 in groups M1, M2 and M3. The rats’ spatial learning and memory abilities were assessed by the Morris Water Maze test at weeks 0, 6, 16, 32, and 48. After week 48, we observed pathological changes in right hippocampal CA1 and CA3 regions, and measured levels of oxidative stress, inflammatory cytokines, and β-amyloid peptide of left hippocampus. Starting from week 6, the serum uric acid level of M3 group > M2 group, the serum uric acid level of M2 group > M1 group, and the serum uric acid level of M1 group > NC group. The rats in M3 and M2 groups had longer escape latencies, longer mean distances to the platform, more extensive pathological damage, stronger inflammation response, higher oxidative stress and β-amyloid peptide levels than those in NC group. No significant differences were observed between M1 and NC groups. In addition, we also found that oxidative stress significantly correlated with tumour necrosis factor-α and β-amyloid peptide. Long-term elevated serum uric acid was significantly associated with cognitive impairment risk. Oxidative stress, tumour necrosis factor-α and β-amyloid peptide may mediate the pathogenesis of the cognitive impairment induced by uric acid. The detrimental effect of elevated serum uric acid on cognitive function was probably expressed when the serum uric acid concentration reached a certain level.
