State Key Laboratory of Food Nutrition and Safety, Tianjin University of Science and Technology, Tianjin 300457, China.
Food Funct. 2020 Feb 26;11(2):1572-1584. doi: 10.1039/c9fo02103e.
Alzheimer's disease, characterized by neuroinflammation and beta-amyloid protein plaques, is a memory-threatening neurodegenerative disease with no effective treatment. Here, the effect of bilberry anthocyanins (BA) on cognitive functions was evaluated using APP/PSEN1 transgenic Alzheimer's disease model mice and their WT littermates. Our results revealed that BA appreciably improves learning and memory abilities and reverses defects to cognitive functions in APP/PSEN1 mice. Furthermore, BA reverses brain, liver and kidney damage caused by Alzheimer's disease, with no significant changes in oxidative stress and lipid metabolism-related indicators. In addition, BA decreases serum and brain lipopolysaccharide (LPS) levels and increases fecal short-chain fatty acid content. Immunofluorescence and RT-PCR analysis results showed that BA fully activates the microglia and astrocytes, downregulates the expression of inflammatory factors (TNF-α, NF-Kβ, IL-1β, IL-6, COX-2, iNOS and CD33) and chemokine receptor CX3CR1, and upregulates the expression of microglia homeostatic factors (TREM2 and TYROBP) and Toll-like receptors (TLR2 and TLR4). Moreover, western blot analysis revealed that BA significantly upregulates the expression of synaptic and phagocytotic function-related proteins (CD68, synaptophysin and IRF7) in APP/PSEN1 mice. Altogether, we show for the first time that BA consumption reverses Alzheimer's disease-induced cognitive disfunction, decreases hippocampal neuroinflammatory responses, and induces phagocytosis of microglia to beta-amyloid protein plaques by regulating the CD33/TREM2/TYROBP signaling pathway in microglia.
阿尔茨海默病（Alzheimer's disease）以神经炎症和β-淀粉样蛋白斑块为特征，是一种威胁记忆的神经退行性疾病，目前尚无有效的治疗方法。在这里，我们使用 APP/PSEN1 转基因阿尔茨海默病模型小鼠及其 WT 同窝仔鼠评估了越橘花色苷（bilberry anthocyanins，BA）对认知功能的影响。我们的结果表明，BA 可显著改善 APP/PSEN1 小鼠的学习和记忆能力，并逆转其认知功能缺陷。此外，BA 可逆转阿尔茨海默病引起的脑、肝和肾损伤，而对氧化应激和脂质代谢相关指标无明显影响。此外，BA 可降低血清和脑组织中的脂多糖（lipopolysaccharide，LPS）水平，并增加粪便中短链脂肪酸的含量。免疫荧光和 RT-PCR 分析结果表明，BA 可完全激活小胶质细胞和星形胶质细胞，下调炎症因子（TNF-α、NF-Kβ、IL-1β、IL-6、COX-2、iNOS 和 CD33）和趋化因子受体 CX3CR1 的表达，上调小胶质细胞稳态因子（TREM2 和 TYROBP）和 Toll 样受体（TLR2 和 TLR4）的表达。此外，Western blot 分析表明，BA 可显著上调 APP/PSEN1 小鼠突触和吞噬功能相关蛋白（CD68、突触素和 IRF7）的表达。总之，我们首次表明，BA 可通过调节小胶质细胞中的 CD33/TREM2/TYROBP 信号通路逆转阿尔茨海默病引起的认知功能障碍，降低海马神经炎症反应，并诱导小胶质细胞对β-淀粉样蛋白斑块的吞噬作用。
