Department of Pharmacy, Liaocheng People's Hospital, Liaocheng City, China.
Department of Pharmacy, Liaocheng Dongchangfu District Maternal and Child Health Hospital, Liaocheng City, China.
Dement Geriatr Cogn Disord. 2019;48(3-4):154-163. doi: 10.1159/000504800. Epub 2020 Jan 15.
BACKGROUND/AIMS: Obesity is associated with chronic inflammation and cognitive decline, and is considered a major risk factor for neurodegeneration. Meanwhile, neuroinflammation is important in the pathogenesis and progression of neurodegenerative diseases.
In this study, we tested the hypothesis that donepezil would attenuate central inflammation and oxidative damage and improve memory deficit in high-fat diet (HFD)-fed mice. After 16 weeks on a HFD, C57BL/6J mice were given either donepezil (3 mg/kg, i.p.) or saline for 4 weeks in parallel to a control diet (CD) group. Thereafter, the step-through test was used to assess learning and memory function.
In the brain of HFD-fed mice, levels of the proinflammatory cytokines interleukin 16 and tumor necrosis factor α were reduced by donepezil treatment. Similarly, HFD-induced protein levels of advanced glycation end-products and oxidative stress in the brain were significantly decreased by donepezil treatment.
Our results indicate that donepezil may reverse obesity-related central inflammation and oxidative damage and improve memory deficit in HFD-fed mice.
背景/目的：肥胖与慢性炎症和认知能力下降有关，被认为是神经退行性变的主要危险因素。同时，神经炎症在神经退行性疾病的发病机制和进展中起着重要作用。
在这项研究中，我们检验了多奈哌齐（donepezil）可减轻高脂饮食（HFD）喂养小鼠中枢炎症和氧化损伤并改善记忆缺陷的假设。在 HFD 喂养 16 周后，C57BL/6J 小鼠同时给予多奈哌齐（3 mg/kg，腹腔注射）或生理盐水，并行对照饮食（CD）组。之后，采用穿梭箱测试评估学习和记忆功能。
在 HFD 喂养小鼠的大脑中，多奈哌齐治疗可降低促炎细胞因子白细胞介素 1β 和肿瘤坏死因子 α 的水平。同样，多奈哌齐治疗可显著降低 HFD 诱导的大脑中晚期糖基化终产物和氧化应激的蛋白水平。
我们的结果表明，多奈哌齐可能逆转肥胖相关的中枢炎症和氧化损伤，并改善 HFD 喂养小鼠的记忆缺陷。
