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基于电容式电极的氧化还原毒性铁沉积在转基因 AD 小鼠模型中的电场处理:阿尔茨海默病电疗靶向的可行性研究。

Capacitive Electrode-Based Electric Field Treatments on Redox-Toxic Iron Deposits in Transgenic AD Mouse Models: The Electroceutical Targeting of Alzheimer's Disease Feasibility Study.

机构信息

Departments of Biomedical Engineering & Radiology, School of Medicine, Daegu Catholic University, Daegu 42472, Republic of Korea.

Departments of Biochemistry, School of Medicine, Daegu Catholic University, Daegu 42472, Republic of Korea.

出版信息

Int J Mol Sci. 2023 May 31;24(11):9552. doi: 10.3390/ijms24119552.

Abstract

Iron accumulation in the brain accelerates Alzheimer's disease progression. To cure iron toxicity, we assessed the therapeutic effects of noncontact transcranial electric field stimulation to the brain on toxic iron deposits in either the Aβ fibril structure or the Aβ plaque in a mouse model of Alzheimer's disease (AD) as a pilot study. A capacitive electrode-based alternating electric field (AEF) was applied to a suspension of magnetite (FeO) to measure field-sensitized reactive oxygen species (ROS) generation. The increase in ROS generation compared to the untreated control was both exposure-time and AEF-frequency dependent. The frequency-specific exposure of AEF to 0.7-1.4 V/cm on a magnetite-bound Aβ-fibril or a transgenic Alzheimer's disease (AD) mouse model revealed the degradation of the Aβ fibril or the removal of the Aβ-plaque burden and ferrous magnetite compared to the untreated control. The results of the behavioral tests show an improvement in impaired cognitive function following AEF treatment on the AD mouse model. Tissue clearing and 3D-imaging analysis revealed no induced damage to the neuronal structures of normal brain tissue following AEF treatment. In conclusion, our results suggest that the effective degradation of magnetite-bound amyloid fibrils or plaques in the AD brain by the electro-Fenton effect from electric field-sensitized magnetite offers a potential electroceutical treatment option for AD.

摘要

脑内铁积累加速阿尔茨海默病的进展。为了治疗铁毒性,我们评估了非接触性经颅电场刺激对阿尔茨海默病(AD)小鼠模型中 Aβ 纤维结构或 Aβ 斑块中有毒铁沉积的治疗效果,作为一项初步研究。采用基于电容电极的交流电场(AEF)对磁铁矿(FeO)悬浮液进行处理,以测量场敏活性氧物种(ROS)的产生。与未处理的对照组相比,ROS 的产生增加既依赖于暴露时间又依赖于 AEF 频率。AEF 以特定频率暴露于 0.7-1.4 V/cm 对结合有 Aβ 纤维的磁铁矿或转基因 AD 小鼠模型进行处理,与未处理的对照组相比,发现 Aβ 纤维或 Aβ 斑块负担以及亚铁磁铁矿的降解。行为测试的结果表明,在 AD 小鼠模型上进行 AEF 治疗后,认知功能障碍得到改善。组织透明和 3D 成像分析显示,AEF 治疗后正常脑组织的神经元结构没有诱导损伤。总之,我们的结果表明,通过电场敏化磁铁矿的电芬顿效应有效降解 AD 脑中结合的淀粉样纤维或斑块为 AD 提供了一种潜在的电疗治疗选择。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cd8d/10254001/ae99a3108ad0/ijms-24-09552-g001.jpg

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