Effect of 40 Hz pulsed magnetic field on mitochondrial dynamics and heart rate variability in dementia mice_Journal of Biomedical Engineering

Authors：

ZHANG Lifan ^1,4 ,  GENG Duyan ^2,3,4 , XU Guizhi ^2,3,4 , AN Hongxia ^1,4

1. School of Health Sciences and Biomedical Engineering, Hebei University of Technology, Tianjin 300130, P. R. China;
2. State Key Laboratory of Reliability and Intelligence of Electrical Equipment, Hebei University of Technology, Tianjin 300130, P. R. China;
3. Hebei Provincial Key Laboratory of Electromagnetic Field and Electrical Reliability, Hebei University of Technology, Tianjin 300130, P. R. China;
4. Tianjin Key Laboratory of Bioelectromagnetic Technology and Intelligent Health, Hebei University of Technology, Tianjin 300130, P. R. China;

Corresponding?author：

GENG Duyan, Email: dygeng@hebut.edu.cn

Keywords：

Alzheimer’s disease; Extremely low frequency magnetic field; Mitochondrial dynamics; Heart rate variability

DOI：

10.7507/1001-5515.202501061

Video：

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Alzheimer’s disease (AD) is the most common degenerative disease of the nervous system. Studies have found that the 40 Hz pulsed magnetic field has the effect of improving cognitive ability in AD, but the mechanism of action is not clear. In this study, APP/PS1 double transgenic AD model mice were used as the research object, the water maze was used to group dementia, and 40 Hz/10 mT pulsed magnetic field stimulation was applied to AD model mice with different degrees of dementia. The behavioral indicators, mitochondrial samples of hippocampal CA1 region and electrocardiogram signals were collected from each group, and the effects of 40 Hz pulsed magnetic field on mouse behavior, mitochondrial kinetic indexes and heart rate variability (HRV) parameters were analyzed. The results showed that compared with the AD group, the loss of mitochondrial crest structure was alleviated and the mitochondrial dynamics related indexes were significantly improved in the AD + stimulated group (P < 0.001), sympathetic nerve excitation and parasympathetic nerve inhibition were improved, and the spatial cognitive memory ability of mice was significantly improved (P < 0.05). The preliminary results of this study show that 40 Hz pulsed magnetic field stimulation can improve the mitochondrial structure and mitochondrial kinetic homeostasis imbalance of AD mice, and significantly improve the autonomic neuromodulation ability and spatial cognition ability of AD mice, which lays a foundation for further exploring the mechanism of ultra-low frequency magnetic field in delaying the course of AD disease and realizing personalized neurofeedback therapy for AD.

Citation： ZHANG Lifan, GENG Duyan, XU Guizhi, AN Hongxia. Effect of 40 Hz pulsed magnetic field on mitochondrial dynamics and heart rate variability in dementia mice. Journal of Biomedical Engineering, 2025, 42(4): 707-715. doi: 10.7507/1001-5515.202501061 Copy

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2.	Hu Y, Lai J, Wan B, et al. Long-term exposure to ELF-MF ameliorates cognitive deficits and attenuates tau hyperphosphorylation in 3xTg AD mice. Neurotoxicology, 2016, 53: 290-300.
3.	Akbarnejad Z, Esmaeilpour K, Shabani M, et al. Spatial memory recovery in Alzheimer’s rat model by electromagnetic field exposure. Int J Neurosci, 2018, 128(8): 691-696.
4.	Liu X, Zuo H, Wang D, et al. Improvement of spatial memory disorder and hippocampal damage by exposure to electromagnetic fields in an Alzheimer’s disease rat model. PLoS One, 2015, 10(5): e0126963.
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7.	Avila J. Common mechanisms in neurodegeneration. Nat Med, 2010, 16(12): 1372.
8.	Geng D, Wang Y, Gao Z, et al. Effects of Alzheimer’s disease of varying severity on cardiac and autonomic function. Braz J Med Biol Res, 2022, 55: e11504.
9.	陳爾冬. 心率變異性的研究及應用進展. 心血管病學進展, 2014, 35(4): 435-439.
10.	Tiwari R, Kumar R, Malik S, et al. Analysis of heart rate variability and implication of different factors on heart rate variability. Curr Cardiol Rev, 2021, 17(5): e160721189770.
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12.	Lin F, Ren P, Wang X, et al. Cortical thickness is associated with altered autonomic function in cognitively impaired and non-impaired older adults. J Physiol, 2017, 595(22): 6969-6978.
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14.	Morris R G M. Spatial localization does not require the presence of local cues. Learn Motiv, 1981, 12(2): 239-260.
15.	趙憲林, 方秀斌, 李東培. 大鼠血管性癡呆模型制作. 中國醫科大學學報, 2002(3): 8-9,18.
16.	Grubb S C, Churchill G A, Bogue M A. A collaborative database of inbred mouse strain characteristics. Bioinformatics, 2004, 20(16): 2857-2859.
17.	李世杰, 唐俐, 周凡琳, 等. 不同月齡APP/PS1雙轉基因AD小鼠海馬神經元線粒體的動態變化. 重慶醫科大學學報, 2021, 46(10): 1141-1146.
18.	Sprugnoli G, Munsch F, Cappon D, et al. Impact of multisession 40Hz tACS on hippocampal perfusion in patients with Alzheimer’s disease. Alzheimers Res Ther, 2021, 13(1): 203.
19.	Toda T, Ito M, Takeda J I, et al. Extremely low-frequency pulses of faint magnetic field induce mitophagy to rejuvenate mitochondria. Commun Biol, 2022, 5(1): 453.
20.	Ruggiero A, Katsenelson M, Slutsky I. Mitochondria: new players in homeostatic regulation of firing rate set points. Trends Neurosci, 2021, 44(8): 605-618.
21.	Xie Y, Li Y, Nie L, et al. Cognitive enhancement of repetitive transcranial magnetic stimulation in patients with mild cognitive impairment and early Alzheimer’s disease: A systematic review and meta-analysis. Front Cell Dev Biol, 2021, 9: 734046.
22.	Toledo M A, Junqueira L F. Cardiac autonomic modulation and cognitive status in Alzheimer’s disease. Clin Auton Res, 2010, 20(1): 11-17.
23.	Mellings?ter M R, Wyller T B, Ranhoff A H, et al. Reduced sympathetic response to head-up tilt in subjects with mild cognitive impairment or mild Alzheimer’s dementia. Dement Geriatr Cogn Dis Extra, 2015, 5(1): 107-115.
24.	Cheng Y C, Huang Y C, Huang W L. Heart rate variability in individuals with autism spectrum disorders: A meta-analysis. Neurosci Biobehav Rev, 2020, 118: 463-471.
25.	Won D O, Lee B R, Seo K S, et al. Alteration of coupling between brain and heart induced by sedation with propofol and midazolam. PLoS One, 2019, 14(7): e0219238.
26.	Vásquez-Trincado C, Pennanen C, Parra V, et al. Mitochondrial dynamics, mitophagy and cardiovascular disease. J Physiol, 2016, 594(3): 509-525.
27.	歐陽葵, 梁培日, 吳挺國, 等. 極低頻電磁場治療對缺血性腦卒中大鼠的神經保護作用及其機制. 醫學理論與實踐, 2022, 35(24): 4141-4143.
28.	Hadzibegovic S, Nicole O, Andelkovic V, et al. Examining the effects of extremely low-frequency magnetic fields on cognitive functions and functional brain markers in aged mice. Sci Rep, 2025, 15(1): 8365.
29.	Cuccurazzu B, Leone L, Podda M V, et al. Exposure to extremely low-frequency (50Hz) electromagnetic fields enhances adult hippocampal neurogenesis in C57BL/6 mice. Exp Neurol, 2010, 226(1): 173-182.
30.	Zhang Y, Liu X, Zhang J, et al. Short-term effects of extremely low frequency electromagnetic fields exposure on Alzheimer’s disease in rats. Int J Radiat Biol, 2015, 91(1): 28-34.

1. Wu L Y, Zhao Q F, Liu J, et al. Efficient identification of Alzheimer’s brain dynamics with Spatial-Temporal Autoencoder: A deep learning approach for diagnosing brain disorders. Biomed Signal Process Control, 2023, 86(Part A): 104917.
2. Hu Y, Lai J, Wan B, et al. Long-term exposure to ELF-MF ameliorates cognitive deficits and attenuates tau hyperphosphorylation in 3xTg AD mice. Neurotoxicology, 2016, 53: 290-300.
3. Akbarnejad Z, Esmaeilpour K, Shabani M, et al. Spatial memory recovery in Alzheimer’s rat model by electromagnetic field exposure. Int J Neurosci, 2018, 128(8): 691-696.
4. Liu X, Zuo H, Wang D, et al. Improvement of spatial memory disorder and hippocampal damage by exposure to electromagnetic fields in an Alzheimer’s disease rat model. PLoS One, 2015, 10(5): e0126963.
5. Joshi A U, Mochly-Rosen D. Mortal engines: Mitochondrial bioenergetics and dysfunction in neurodegenerative diseases. Pharmacol Res, 2018, 138: 2-15.
6. Moreira P I, Carvalho C, Zhu X, et al. Mitochondrial dysfunction is a trigger of Alzheimer’s disease pathophysiology. Biochim Biophys Acta, 2010, 1802(1): 2-10.
7. Avila J. Common mechanisms in neurodegeneration. Nat Med, 2010, 16(12): 1372.
8. Geng D, Wang Y, Gao Z, et al. Effects of Alzheimer’s disease of varying severity on cardiac and autonomic function. Braz J Med Biol Res, 2022, 55: e11504.
9. 陳爾冬. 心率變異性的研究及應用進展. 心血管病學進展, 2014, 35(4): 435-439.
10. Tiwari R, Kumar R, Malik S, et al. Analysis of heart rate variability and implication of different factors on heart rate variability. Curr Cardiol Rev, 2021, 17(5): e160721189770.
11. Zeki Al Hazzouri A, Haan M N, Deng Y, et al. Reduced heart rate variability is associated with worse cognitive performance in elderly Mexican Americans. Hypertension, 2014, 63(1): 181-187.
12. Lin F, Ren P, Wang X, et al. Cortical thickness is associated with altered autonomic function in cognitively impaired and non-impaired older adults. J Physiol, 2017, 595(22): 6969-6978.
13. 譚如欣, 王欣, 殷濤, 等. 阿爾茲海默癥轉基因鼠生長過程中海馬theta節律及行為學的實驗研究. 生物醫學工程研究, 2020, 39(2): 109-115.
14. Morris R G M. Spatial localization does not require the presence of local cues. Learn Motiv, 1981, 12(2): 239-260.
15. 趙憲林, 方秀斌, 李東培. 大鼠血管性癡呆模型制作. 中國醫科大學學報, 2002(3): 8-9,18.
16. Grubb S C, Churchill G A, Bogue M A. A collaborative database of inbred mouse strain characteristics. Bioinformatics, 2004, 20(16): 2857-2859.
17. 李世杰, 唐俐, 周凡琳, 等. 不同月齡APP/PS1雙轉基因AD小鼠海馬神經元線粒體的動態變化. 重慶醫科大學學報, 2021, 46(10): 1141-1146.
18. Sprugnoli G, Munsch F, Cappon D, et al. Impact of multisession 40Hz tACS on hippocampal perfusion in patients with Alzheimer’s disease. Alzheimers Res Ther, 2021, 13(1): 203.
19. Toda T, Ito M, Takeda J I, et al. Extremely low-frequency pulses of faint magnetic field induce mitophagy to rejuvenate mitochondria. Commun Biol, 2022, 5(1): 453.
20. Ruggiero A, Katsenelson M, Slutsky I. Mitochondria: new players in homeostatic regulation of firing rate set points. Trends Neurosci, 2021, 44(8): 605-618.
21. Xie Y, Li Y, Nie L, et al. Cognitive enhancement of repetitive transcranial magnetic stimulation in patients with mild cognitive impairment and early Alzheimer’s disease: A systematic review and meta-analysis. Front Cell Dev Biol, 2021, 9: 734046.
22. Toledo M A, Junqueira L F. Cardiac autonomic modulation and cognitive status in Alzheimer’s disease. Clin Auton Res, 2010, 20(1): 11-17.
23. Mellings?ter M R, Wyller T B, Ranhoff A H, et al. Reduced sympathetic response to head-up tilt in subjects with mild cognitive impairment or mild Alzheimer’s dementia. Dement Geriatr Cogn Dis Extra, 2015, 5(1): 107-115.
24. Cheng Y C, Huang Y C, Huang W L. Heart rate variability in individuals with autism spectrum disorders: A meta-analysis. Neurosci Biobehav Rev, 2020, 118: 463-471.
25. Won D O, Lee B R, Seo K S, et al. Alteration of coupling between brain and heart induced by sedation with propofol and midazolam. PLoS One, 2019, 14(7): e0219238.
26. Vásquez-Trincado C, Pennanen C, Parra V, et al. Mitochondrial dynamics, mitophagy and cardiovascular disease. J Physiol, 2016, 594(3): 509-525.
27. 歐陽葵, 梁培日, 吳挺國, 等. 極低頻電磁場治療對缺血性腦卒中大鼠的神經保護作用及其機制. 醫學理論與實踐, 2022, 35(24): 4141-4143.
28. Hadzibegovic S, Nicole O, Andelkovic V, et al. Examining the effects of extremely low-frequency magnetic fields on cognitive functions and functional brain markers in aged mice. Sci Rep, 2025, 15(1): 8365.
29. Cuccurazzu B, Leone L, Podda M V, et al. Exposure to extremely low-frequency (50Hz) electromagnetic fields enhances adult hippocampal neurogenesis in C57BL/6 mice. Exp Neurol, 2010, 226(1): 173-182.
30. Zhang Y, Liu X, Zhang J, et al. Short-term effects of extremely low frequency electromagnetic fields exposure on Alzheimer’s disease in rats. Int J Radiat Biol, 2015, 91(1): 28-34.

Journal of Biomedical Engineering

Effect of 40 Hz pulsed magnetic field on mitochondrial dynamics and heart rate variability in dementia mice

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