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| Hyperuricemia accelerate Aβ deposition in rat hippocampus and the related mechanisms#br# |
| ZHOU Meng1, CHEN Zhihan1, ZHENG Weiping2, DAI Yijun1, GAO Fei1, YAN Qing1 |
(1. Department of Rheumatology and Immunology, 2. Department of Geriatric Medicine, Fujian Provincial Hospital, Fuzhou Fujian 350001, China)
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Abstract Objective： To investigate the effects of serum uric acid levels on cognitive function and Aβ expression in hippocampus of rats, and to explore the related mechanisms. Methods： Twentyfour Wistar male rats were randomly divided into control group, lowdose model group, middledose model group and highdose model group, with 6 rats in each group. The hyperuricemia animal model was established by using yeast extract feed combined with different concentrations of potassium oxonate intraperitoneal injection for 4 weeks. The learning and memory ability of the rats in each group was tested by Morris water maze. The expression levels of Aβ and key proteins in Aβ production and clearance pathways in the hippocampus of rats in each group were detected by ELLISA and Western blotting assays. Results： Compared with the control group, the level of uric acid in each model group was significantly increased (P<0.01). And there was no significant difference in the number of times of crossing the platform and the time spent in the quadrant of the platform in each group. Compared with control group, the expression levels of Aβ142, amyloid precursor protein (APP), βsite APP cleaving enzyme 1 (BACE1), neprilysin (NEP) and insulin degrading enzyme (IDE) were increased in model groups, and the expression levels increased with the raise of serum uric acid level. However, the expression of ABCG2 was decreased in model group, and gradually decreased with the increase of serum uric acid level. Conclusion： Hyperuricemia can aggravate Aβ deposition in rat hippocampus, possibly through the APPBACE1 pathway to increase the production of Aβ or/and the ABCG2 pathway to reduce the clearance of Aβ, rather than through NEP, IDE degradation pathways. Hyperuricemia had no significant effect on cognitive function.
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Received: 17 June 2022
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