Department of Neurology, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325027, People's Republic of China.
Department of Preventive Medicine, School of Public Health and Management, Wenzhou Medical University, Wenzhou, Zhejiang 325035, People's Republic of China.
J Agric Food Chem. 2020 Jul 8;68(27):7152-7161. doi: 10.1021/acs.jafc.0c02807. Epub 2020 Jun 25.
Alzheimer's disease (AD) is a high-incidence neurodegenerative disease in the elderly. Acetate (Ace) is a short-chain fatty acid (SCFA) with neuroprotective activity. The purpose of this study was to investigate the effects and its possible mechanisms of SCFA Ace on AD. A male APP/PS1 transgenic mouse was given intragastric administration Ace for 4 weeks. Cognitive function and microglia activation in mice were assessed. Furthermore, Ace pretreated amyloid-β (Aβ)-induced BV2 microglia, and the levels of CD11b, COX-2, and G-protein-coupled receptor 41 (GPR41) and phosphorylation of ERK, JNK, and NF-κB p65 were determined. Our results revealed that Ace significantly attenuated the cognitive impairment and decreased the CD11b level in the APP/PS1 mice. Moreover, Ace inhibited the phosphorylation of NF-κB p65, ERK, and JNK and decreased the levels of COX-2 and interleukin 1β in the Aβ-stimulated BV2 microglia. Finally, Ace increased the GPR41 level in the Aβ-stimulated BV2 cells. The finding indicated that Ace exerted antineuroinflammatory effects via the upregulation of GPR41 and suppression of the ERK/JNK/NF-κB pathway, which might provide an alternative therapy strategy of AD.
阿尔茨海默病（AD）是一种高发于老年人的神经退行性疾病。醋酸盐（Ace）是一种具有神经保护活性的短链脂肪酸（SCFA）。本研究旨在探讨 SCFA Ace 对 AD 的作用及其可能机制。雄性 APP/PS1 转基因小鼠给予 Ace 灌胃 4 周，评估小鼠的认知功能和小胶质细胞激活情况。此外，Ace 预处理淀粉样β（Aβ）诱导的 BV2 小胶质细胞，测定 CD11b、COX-2 和 G 蛋白偶联受体 41（GPR41）水平以及 ERK、JNK 和 NF-κB p65 的磷酸化水平。结果表明，Ace 显著减轻了 APP/PS1 小鼠的认知障碍，降低了 CD11b 水平。此外，Ace 抑制了 NF-κB p65、ERK 和 JNK 的磷酸化，并降低了 Aβ刺激的 BV2 小胶质细胞中 COX-2 和白细胞介素 1β的水平。最后，Ace 增加了 Aβ刺激的 BV2 细胞中 GPR41 的水平。这些发现表明，Ace 通过上调 GPR41 和抑制 ERK/JNK/NF-κB 通路发挥抗炎作用，这可能为 AD 提供一种替代的治疗策略。
