对雄性APP/PS1转基因小鼠乙酸盐灌胃给药4 周。评估小鼠的认知功能和小胶质细胞活化。此外，乙酸盐预处理淀粉样β（Aβ）诱导的BV2小胶质细胞，并测定了CD11b、COX-2和G蛋白偶联受体41（GPR41）的水平以及ERK、JNK和NF-κBp65的磷酸化。我们的结果表明，乙酸盐可显着缓解APP/PS1小鼠的认知障碍并降低CD11b水平。此外，乙酸盐可抑制Aβ诱导的BV2小胶质细胞中NF-κBp65、ERK和JNK的磷酸化，并降低了COX-2和白介素1β的水平。最后，乙酸盐提高了Aβ诱导的BV2细胞中的GPR41水平。
该发现表明乙酸盐通过上调GPR41和抑制ERK/JNK/NF-κB通路发挥抗神经炎症作用，这可能为阿尔茨海默病提供了另一种治疗策略。
Abstract
Anti-neuroinflammatory Effect of Short-Chain Fatty Acid Acetate against Alzheimer’s Disease via Upregulating GPR41 and Inhibiting ERK/JNK/NF-κB
Jiaming Liu, Haijun Li, Tianyu Gong, Wenyang Chen, Shiyin Mao, Yu Kong, Jiaheng Yu, and Jing Sun*
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.
