School of Basic Medical Sciences, Zhejiang Chinese Medical University, Hangzhou, China.
School of Basic Medical Sciences, Zhejiang Chinese Medical University, Hangzhou, China.
J Chromatogr B Analyt Technol Biomed Life Sci. 2023 May 30;1224:123766. doi: 10.1016/j.jchromb.2023.123766. Epub 2023 May 26.
Accumulated clinical and biomedical evidence suggests that abnormalities in systemic metabolic processes such as fatty acid and amino acid metabolism can affect the brain function and behavior of various central nervous system diseases such as Alzheimer's disease (AD). In this study, metabolic profiling was used to investigate changes in plasma and urine metabolites following stereotactic injection of amyloid β (Aβ) and treatment with donepezil in rats. Aβ causes cognitive impairment, while donepezil treatment successfully improves memory impairment. Donepezil improves Aβ-induced plasma fatty acid and bile acid metabolism disorders, as well as Aβ-induced urine phenylalanine and tryptophan metabolism disorders in rats. More specifically, the plasma fatty acids improved by donepezil include alpha-linolenic acid, stearidonic acid, eicosapentaenoic acid, docosahexaenoic acid, linoleic acid, arachidonic acid, oleic acid, and palmitic acid, among others. Additionally, donepezil significantly restored the downregulation of bile acids such as ursodeoxycholic acid, cholic acid, and glycocholic acid caused by Aβ. As for urine metabolites, phenylacetylglycine, epinephrine, and other phenylalanine metabolites, as well as kynurenic acid, xanthurenic acid, and other tryptophan metabolites, were worsened by Aβ and improved by donepezil. These findings suggest that the cognitive impairment induced by Aβ and the improvement by donepezil are associated with changes in metabolic disorders in rats. This study provides basic data for the effects of Aβ and donepezil on plasma and urine metabolites in Aβ-induced AD rat models.
临床和生物医学证据积累表明，脂肪酸和氨基酸代谢等系统性代谢过程的异常会影响各种中枢神经系统疾病（如阿尔茨海默病，AD）的大脑功能和行为。在这项研究中，采用代谢组学方法研究了淀粉样蛋白β（Aβ）立体定向注射后以及多奈哌齐治疗后大鼠血浆和尿液代谢物的变化。Aβ 可导致认知障碍，而多奈哌齐治疗可成功改善记忆障碍。多奈哌齐可改善 Aβ 诱导的大鼠血浆脂肪酸和胆汁酸代谢紊乱，以及 Aβ 诱导的尿液苯丙氨酸和色氨酸代谢紊乱。具体而言，多奈哌齐改善的血浆脂肪酸包括α-亚麻酸、二十碳五烯酸、二十二碳六烯酸、亚油酸、花生四烯酸、油酸和棕榈酸等。此外，多奈哌齐还显著恢复了 Aβ 引起的熊去氧胆酸、胆酸和甘氨胆酸等胆汁酸的下调。至于尿液代谢物，苯乙酰甘氨酸、肾上腺素等苯丙氨酸代谢物，以及犬尿氨酸、黄尿酸等色氨酸代谢物，均因 Aβ 而恶化，而被多奈哌齐改善。这些发现表明，Aβ 引起的认知障碍和多奈哌齐的改善与大鼠代谢紊乱的变化有关。本研究为 Aβ 和多奈哌齐对 Aβ 诱导的 AD 大鼠模型血浆和尿液代谢物的影响提供了基础数据。
