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旋转磁场通过调节小胶质细胞极化改善散发性 AD 模型小鼠的认知和记忆障碍。

Rotating magnetic field improved cognitive and memory impairments in a sporadic ad model of mice by regulating microglial polarization.

机构信息

Shenzhen University School of Basic Medical Sciences, Shenzhen, 518055, Guangdong, China.

Shenzhen University College of Medicine, Shenzhen, 518055, Guangdong, China.

出版信息

Geroscience. 2024 Dec;46(6):6229-6256. doi: 10.1007/s11357-024-01223-y. Epub 2024 Jun 21.

Abstract

Neuroinflammation, triggered by aberrantly activated microglia, is widely recognized as a key contributor to the initiation and progression of Alzheimer's disease (AD). Microglial activation in the central nervous system (CNS) can be classified into two distinct phenotypes: the pro-inflammatory M1 phenotype and the anti-inflammatory M2 phenotype. In this study, we investigated the effects of a non-invasive rotating magnetic field (RMF) (0.2T, 4Hz) on cognitive and memory impairments in a sporadic AD model of female Kunming mice induced by AlCl and D-gal. Our findings revealed significant improvements in cognitive and memory impairments following RMF treatment. Furthermore, RMF treatment led to reduced amyloid-beta (Aβ) deposition, mitigated damage to hippocampal morphology, prevented synaptic and neuronal loss, and alleviated cell apoptosis in the hippocampus and cortex of AD mice. Notably, RMF treatment ameliorated neuroinflammation, facilitated the transition of microglial polarization from M1 to M2, and inhibited the NF-кB/MAPK pathway. Additionally, RMF treatment resulted in reduced aluminum deposition in the brains of AD mice. In cellular experiments, RMF promoted the M1-M2 polarization transition and enhanced amyloid phagocytosis in cultured BV2 cells while inhibiting the TLR4/NF-кB/MAPK pathway. Collectively, these results demonstrate that RMF improves memory and cognitive impairments in a sporadic AD model, potentially by promoting the M1 to M2 transition of microglial polarization through inhibition of the NF-кB/MAPK signaling pathway. These findings suggest the promising therapeutic applications of RMF in the clinical treatment of AD.

摘要

神经炎症是由异常激活的小胶质细胞触发的,被广泛认为是阿尔茨海默病(AD)发病和进展的关键因素。中枢神经系统(CNS)中小胶质细胞的激活可分为两种截然不同的表型:促炎 M1 表型和抗炎 M2 表型。在这项研究中,我们研究了非侵入性旋转磁场(RMF)(0.2T,4Hz)对 AlCl 和 D-半乳糖诱导的雌性昆明 AD 模型小鼠认知和记忆障碍的影响。我们的研究结果表明,RMF 治疗可显著改善认知和记忆障碍。此外,RMF 治疗可减少淀粉样蛋白-β(Aβ)沉积,减轻海马形态损伤,防止突触和神经元丢失,并减轻 AD 小鼠海马和皮质中的细胞凋亡。值得注意的是,RMF 治疗可改善神经炎症,促进小胶质细胞极化从 M1 向 M2 转变,并抑制 NF-кB/MAPK 通路。此外,RMF 治疗可减少 AD 小鼠大脑中的铝沉积。在细胞实验中,RMF 促进了培养的 BV2 细胞中 M1-M2 极化的转变,并增强了对淀粉样蛋白的吞噬作用,同时抑制了 TLR4/NF-кB/MAPK 通路。综上所述,这些结果表明 RMF 通过抑制 NF-кB/MAPK 信号通路促进小胶质细胞极化从 M1 向 M2 的转变,改善了散发性 AD 模型中的记忆和认知障碍。这些发现表明 RMF 在 AD 的临床治疗中有很好的应用前景。

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