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The detrimental effects of long-term elevated serum uric acid on cognitive function in rats

Tian Tian  Xi-run Liu  Ting-ting Li  Zhi-chao Nie  Shuang-jing Li  Yan Tang  Cong-wei Gu  Wang-dong Xu  Hong Jia  
【摘要】:Background:Uric acid,a powerful antioxidant,may have neuroprotective properties.But elevated serum uric acid is association with cardiovascular diseases that predispose individuals to cognitive impairment.Findings from studies on uric acid and cognitive function were inconsistent.The effects of uric acid on cognitive function may be related to the concentration and exposure period of uric acid.Therefore,we aimed to explore the effects of long-term elevated serum uric acid on the cognitive function and hippocampus.Methods:The hyperuricemia rats were successfully established at 6~(th) week and maintained until 48~(th) week.Serum uric acid level was measured in blood sample of rat.The spatial learning and memory abilities of rat were assessed by Moris Water Maze test.The pathological changes of hippocampal CA1 and CA3 regions of rat were observed.Oxidative stress,inflammatory cytokines and β-amyloid peptide of rat hippocampus were also measured.Results:Long-term elevated serum uric acid impaired the spatial learning ability of rat and was significantly associated with pathological injuries of hippocampal CA1 and CA3 regions.Meanwhile,long-term elevated serum uric acid induced oxidativu stress,and overexpression of tumor necrosis factor-α and β-amyloid peptide in rat hippocampus.Oxidative stress was significantly correlated with tumor necrosis factor-α and β-amyloid peptide levels in rat hippocampus.In addition,we also found that the detrimental effects of elevated serum uric acid on cognitive function exerted only when the serum uric acid concentration reached a certain level.Conclusion:Findings of our study indicated that long-term elevated serum uric acid was significantly associated with cognitive impairment risk.Oxidative stress,tumor necrosis factor-α and β-amyloid peptide may mediate the pathogenesis of cognitive impairment induced by uric acid.

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