ELF-MF对AD小鼠Aβ<sub>42</sub>沉积及SWM相关神经振荡的影响

耿读艳; 刘澳格; 闫禹新; 郑卫然

doi:10.11999/JEIT241106

ELF-MF对AD小鼠Aβ₄₂沉积及SWM相关神经振荡的影响

doi: 10.11999/JEIT241106 cstr: 32379.14.JEIT241106

耿读艳^{1, 3, ,},
刘澳格²,
闫禹新¹,
郑卫然¹

1.
河北工业大学电气工程学院天津 300130
2.
河北工业大学生命科学与健康工程学院天津 300130
3.
省部共建电工装备可靠性与智能化国家重点实验室(河北工业大学) 天津 300130

基金项目: 国家自然科学基金(No.52277230)

详细信息

作者简介:
耿读艳：男，博士，教授，研究方向为生物电磁技术

刘澳格：女，硕究生，研究方向为生物电磁与神经调控

闫禹新：男，研究生，研究方向为脑认知与神经工程

郑卫然：男，博士生，研究方向为生物电磁与神经调控

通讯作者:
耿读艳　dygeng@hebut.edu.cn

中图分类号: TN911.7; R318; R338
计量
- 文章访问数: 5
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- PDF下载量: 2
- 被引次数: 0
出版历程
- 修回日期: 2025-10-13
- 网络出版日期: 2025-10-20

The effects of ELF-MF on Aβ₄₂ deposition in AD mice and SWM-related neural oscillations

GENG Duyan^{1, 3
, ,},
LIU Aoge²,
YAN Yuxin¹,
ZHENG Weiran¹

1.
School of Electrical Engineering, Hebei University of Technology, Tianjin 300130, China
2.
School of Life Science and Health Engineering, Hebei University of Technology, Tianjin 300130, China
3.
State Key Laboratory of Reliability and Intelligence of Electrical Equipment, Hebei University of Technology, Tianjin 300130, China

Funds: The National Natural Science Foundation of China (52277230)

摘要

摘要: 极低频磁场(ELF-MF)已被证实可以对多种常见疾病产生积极影响，但其对阿尔茨海默病(AD)的影响仍然知之甚少。该文将免疫荧光检测、行为学和电生理学相结合，通过计算完成对象位置任务(OLT)的行为认知指数(CI)，探究ELF-MF暴露对小鼠空间工作记忆(SWM)的影响；应用时频分布和相位-幅值耦合分析方法，探究小鼠进行OLT过程中海马CA1区局部场电位信号(LFPs)的theta频段和gamma频段神经振荡的变化规律；进一步通过免疫荧光技术定量分析了小鼠海马区域Aβ₄₂的沉积情况，探究ELF-MF暴露对AD病理标志物的影响。此外，还分析了CI与海马CA1区theta频段和gamma频段神经振荡的时频分布及相位-幅值耦合之间的相关性，旨在探究ELF-MF对认知功能和神经振荡模式的调控机制。结果表明，ELF-MF可以减少AD小鼠海马区Aβ₄₂含量，增强AD模型小鼠的SWM能力，且这种增强与小鼠SWM任务期间海马CA1区theta和gamma频段神经振荡的时频能量以及theta-gamma相位-幅值耦合增强有关。
- 极低频磁场 /
- 阿尔兹海默病 /
- 空间工作记忆 /
- 神经振荡 /
- 淀粉样蛋白-β
Abstract: Objective Extremely low-frequency magnetic fields (ELF-MF) have demonstrated beneficial effects for various common diseases, yet their impact on Alzheimer's disease (AD) remains poorly understood. With the accelerating aging of the global population, Alzheimer's disease has become one of the most prevalent neurodegenerative disorders. AD features complex pathogenesis, with primary pathological changes including neuronal loss, extracellular amyloid-β (Aβ) deposition, and intracellular neurofibrillary tangles. One of the main clinical manifestations is cognitive decline, particularly spatial working memory (SWM) impairment. As a crucial cognitive function for processing and remembering spatial location information, SWM is essential for executing complex cognitive tasks. SWM dysfunction not only significantly affects patients' daily lives but also serves as a key indicator for assessing AD progression. While previous studies have suggested potential cognitive benefits of ELF-MF, systematic investigations integrating pathological, behavioral, and electrophysiological approaches are lacking. This study aims to systematically investigate whether 40 Hz ELF-MF exposure can ameliorate AD pathology by examining Aβ₄₂ deposition, SWM performance, and neural oscillatory activities in the hippocampal CA1 region, while exploring the relationships between electrophysiological changes and behavioral improvements. Methods The study employed an integrated multidisciplinary approach combining immunofluorescence detection, behavioral assessment, and electrophysiological recording. Transgenic AD model mice and wild-type controls were utilized and divided into three experimental groups: wild-type controls (Con), AD model group (AD), and AD model group receiving ELF-MF stimulation (ES). The ES group received 40 Hz, 10 mT continuous pulse stimulation twice daily for 0.5 hours each session over 14 consecutive days, while the AD and Con groups underwent sham stimulation during identical time periods. Spatial working memory was evaluated using the object location task (OLT), with behavioral performance quantitatively assessed by calculating the cognitive index (CI) that measures the animal's ability to detect spatial novelty. During behavioral testing, synchronous electrophysiological recordings were obtained from the hippocampal CA1 region using chronically implanted microelectrodes to acquire local field potential (LFP) signals. Advanced signal processing techniques including time-frequency distribution analysis and phase-amplitude coupling calculations were applied to characterize neural oscillations in theta (4-13 Hz) and gamma (30-80 Hz) frequency bands. Post-experiment, mouse brain tissues were collected for quantitative measurement of Aβ₄₂ plaque deposition in hippocampal sections through immunofluorescence staining using standardized imaging and quantification protocols. Comprehensive statistical analyses were performed to examine correlations between behavioral performance indicators and various electrophysiological parameters to identify potential mechanistic relationships underlying ELF-MF effects. Results and Discussions Experimental results demonstrated that 40 Hz ELF-MF exposure produced significant therapeutic effects across all examined parameters. Pathological analysis revealed substantially reduced Aβ₄₂ deposition levels in the hippocampal region of treated AD mice compared to untreated controls, supporting the amyloid cascade hypothesis which posits Aβ oligomers as key factors triggering neurodegeneration. This reduction suggests ELF-MF may modulate Aβ metabolic pathways, potentially through regulating mitochondrial dynamics as indicated by previous research. Behavioral assessment showed marked improvement in spatial working memory performance following ELF-MF exposure, as evidenced by significantly elevated cognitive index scores in the object location task. Electrophysiological recordings revealed substantial modifications in neural oscillatory patterns, with treated animals exhibiting increased power spectral density in both theta and gamma frequency bands during memory task performance. Notably, the temporal dynamics of theta oscillations differed significantly between groups: Con and ES groups showed peak theta power occurring approximately 0.5-1 seconds before the behavioral reference point, suggesting anticipatory processing, while the AD group displayed peaks after the reference point, indicating delayed cognitive processing. Furthermore, cross-frequency coupling analysis demonstrated enhanced theta-gamma phase-amplitude coupling strength in the hippocampal CA1 region of ELF-MF exposed animals, with coupling peaks primarily observed in the lower theta frequencies and higher gamma frequencies. Correlation analyses established statistically significant positive relationships between behavioral cognitive indices and electrophysiological measurements, particularly strong for theta power and theta-gamma coupling strength. These coordinated improvements across pathological, behavioral, and electrophysiological domains suggest that ELF-MF exposure functions through restoring impaired neural synchronization mechanisms. The enhanced theta-gamma cross-frequency coupling is particularly significant as this neurophysiological mechanism supports temporal coordination of neuronal assemblies during memory processes. While our findings demonstrate clear benefits, we acknowledge the existing heterogeneity in ELF-MF research outcomes, which may depend on critical parameters including frequency, intensity, duration, and exposure intervals. Previous studies have reported varying effects: some showing no significant impact or even impaired memory consolidation with different stimulation parameters, while others demonstrate cognitive improvement. This parameter dependency presents challenges for clinical translation and highlights the need for systematic optimization in higher animal models. Conclusions This comprehensive investigation demonstrates that 40 Hz extremely low-frequency magnetic field exposure effectively reduces Aβ₄₂ deposition in the hippocampal region of AD mice, ameliorates spatial working memory deficits, and normalizes neural oscillatory activities in the hippocampal CA1 region. The cognitive improvements are closely associated with the enhancement of oscillations in theta and gamma frequency bands and the strengthening of theta-gamma cross-frequency coupling, suggesting that neuromodulatory effects on neural synchronization mechanisms underlie behavioral recovery. These findings provide compelling evidence for the potential application of ELF-MF as a non-invasive therapeutic intervention for Alzheimer's disease, simultaneously targeting both pathological markers and functional impairments. The study establishes a solid foundation for future research aimed at optimizing stimulation parameters and translating these findings to clinical applications, while also highlighting the importance of neural oscillatory restoration as a therapeutic mechanism in neurodegenerative disorders. Future investigations should focus on parameter optimization and developing personalized stimulation protocols to account for individual variability in treatment response.
- Extremely low-frequency magnetic field (ELF-MF) /
- Alzheimer's disease (AD) /
- spatial working memory (SWM) /
- nerve oscillations /
- Amyloid-β (Aβ)

HTML全文

图 1 ELF-MF刺激仪及电场仿真图

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图 2 OLT实验

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图 3 Aβ₄₂免疫荧光及面积百分比图

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图 4 平均CI(%)

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图 5 Theta频段

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图 6 Gamma频段

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图 7 Theta-Gamma相位-幅值耦合

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图 8 相关性散点图

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