Innovation Center for Neurological Disorders and Department of Neurology, Xuanwu Hospital, Capital Medical University, National Clinical Research Center for Geriatric Diseases, Beijing, P.R. China.
Beijing Key Laboratory of Geriatric Cognitive Disorders, Beijing, P.R. China.
J Alzheimers Dis. 2023;94(s1):S9-S19. doi: 10.3233/JAD-230064.
Microglia-driven neuroinflammation has been shown to be involved in the entire process of Alzheimer's disease (AD). Betaine is a natural product that exhibits anti-inflammatory activity; however, the exact underlying molecular mechanisms are poorly understood.
Our study focused on determining the effect of betaine against amyloid-β42 oligomer (AβO)-induced inflammation in microglial BV2 cells and investigating the underlying mechanism.
AβO was used to establish an in vitro AD model using BV2 cells. A 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide assay was used to measure BV2 cell viability with different concentrations of AβO and betaine. Reverse transcription-polymerase chain reaction and enzyme-linked immunosorbent assays were used to determine the expression levels of inflammatory factors, such as interleukin-1β (IL-1β), interleukin-18 (IL-18), and tumor necrosis factor α (TNF-α). Western blotting was used to evaluate the activation of the NOD-like receptor pyrin domain containing-3 (NLRP3) inflammasome and nuclear transcription factor-κB p65 (NF-κB p65). Moreover, we used phorbol 12-myristate 13-acetate (PMA) to activate NF-κB in order to validate that betaine exerted anti-neuroinflammatory effects through regulation of the NF-κB/NLRP3 signaling pathway.
We used 2 mM betaine to treat 5μM AβO-induced microglial inflammation. The administration of betaine effectively decreased the levels of IL-1β, IL-18, and TNF-α without affecting cell viability in BV2 microglial cells.
Betaine inhibited AβO-induced neuroinflammation in microglia by inhibiting the activation of the NLRP3 inflammasome and NF-κB, which supports further evaluation of betaine as a potential effective modulator for AD.
小胶质细胞驱动的神经炎症已被证明参与了阿尔茨海默病（AD）的整个过程。甜菜碱是一种具有抗炎活性的天然产物；然而，其确切的潜在分子机制尚不清楚。
本研究旨在确定甜菜碱对小胶质细胞 BV2 细胞中淀粉样蛋白-β42 寡聚体（AβO）诱导的炎症的影响，并探讨其潜在机制。
用 AβO 建立 BV2 细胞体外 AD 模型。采用 3-(4,5-二甲基噻唑-2-基)-2,5-二苯基-2H-四唑溴盐法测定不同浓度 AβO 和甜菜碱对 BV2 细胞活力的影响。逆转录-聚合酶链反应和酶联免疫吸附试验测定白细胞介素-1β（IL-1β）、白细胞介素-18（IL-18）和肿瘤坏死因子-α（TNF-α）等炎症因子的表达水平。Western blot 法评价 NOD 样受体含吡咯烷结构域蛋白 3（NLRP3）炎症小体和核转录因子-κB p65（NF-κB p65）的激活情况。此外，我们用佛波醇 12-肉豆蔻酸 13-醋酸酯（PMA）激活 NF-κB，以验证甜菜碱通过调节 NF-κB/NLRP3 信号通路发挥抗神经炎症作用。
我们用 2mmol/L 甜菜碱处理 5μM AβO 诱导的小胶质细胞炎症。给予甜菜碱可有效降低 BV2 小胶质细胞中 IL-1β、IL-18 和 TNF-α的水平，而不影响细胞活力。
甜菜碱通过抑制 NLRP3 炎症小体和 NF-κB 的激活抑制 AβO 诱导的小胶质细胞神经炎症，这支持进一步评估甜菜碱作为 AD 潜在有效调节剂的可能性。
