High uric acid induced hippocampal mitochondrial dysfunction and cognitive impairment involving intramitochondrial NF-kappa B inhibitor alpha/nuclear factor-kappa B pathway

Objectives Epidemiological research has indicated that hyperuricemia may impair cognitive ability; however, the underlying mechanisms remain unclear. The present study thus investigated the possible mechanism underlying hyperuricemia-related cognitive impairment. Methods Using hyperuricemic rats and high uric acid (UA) intracerebroventricularly treated mice, the current study elucidated whether and how high UA impaired cognitive ability and hippocampal mitochondrial bioenergetic function. Results Hyperuricemia induced UA uptake by hippocampal mitochondria, which impaired cognitive ability and disrupted the bioenergetic function of hippocampal mitochondria, indicated by reduced ATP production and decreased cytochrome c oxidase (COX) activity. Mechanistically. excess UA might trigger intramitochondrial NF-kappa B inhibitor alpha (I kappa B alpha)/nuclear factor-kappa B (NF-kappa B) pathway to downregulate the subunit III of COX (COXIII). Conclusion The results provided new insights into the mechanism underlying hyperuricemia-related cognitive decline. (C) 2022 Wolters Kluwer Health, Inc. All rights reserved.