Long-term electroacupuncture and repetitive transcranial magnetic stimulation differentially slow the progression of Alzheimer's disease in App NL−G−F mice

Abstract Both electroacupuncture (EA) and repetitive transcranial magnetic stimulation (rTMS) possess the potential in combating the progression of Alzheimer’s disease (AD). In this study, we compared the effects of the two regimens as early long-term intervention in App NL−G−F mice, a new amyloid p...

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Main Authors: Si-Min Song, Qian-Min Liu, Xi Huang, Ping Chen, Min Tao, Xia Pei, Hua-Ning Wang, Yan Han, Jian-Guo Chen, Wei Hong, Zhang-Jin Zhang
Format: Article
Language:English
Published: BMC 2025-06-01
Series:Alzheimer’s Research & Therapy
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Online Access:https://doi.org/10.1186/s13195-025-01781-z
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author Si-Min Song
Qian-Min Liu
Xi Huang
Ping Chen
Min Tao
Xia Pei
Hua-Ning Wang
Yan Han
Jian-Guo Chen
Wei Hong
Zhang-Jin Zhang
author_facet Si-Min Song
Qian-Min Liu
Xi Huang
Ping Chen
Min Tao
Xia Pei
Hua-Ning Wang
Yan Han
Jian-Guo Chen
Wei Hong
Zhang-Jin Zhang
author_sort Si-Min Song
collection DOAJ
description Abstract Both electroacupuncture (EA) and repetitive transcranial magnetic stimulation (rTMS) possess the potential in combating the progression of Alzheimer’s disease (AD). In this study, we compared the effects of the two regimens as early long-term intervention in App NL−G−F mice, a new amyloid precursor protein (APP) knock-in model that recapitulates multiple AD-associated pathologies, including amyloid-β (Aβ) plaques, microgliosis, astrocytosis, dendritic and synaptic degeneration. The 2-month-old freely moving model mice randomly received EA or rTMS for 2~3 sessions a week for 6 months. Cognitive tests were conducted in Y maze and Barnes maze sequentially at the age of 4, 6, and 8 months. The cortex and hippocampus were dissected thereafter for neurohistological and molecular analysis. Both regimens markedly prevented cognitive deterioration at 6 months old. EA maintained its significant prevention to 8 months old, but rTMS did not. At this age, EA remarkably reduced Aβ burdens with particular dense-core plaques; rTMS had similar effects on Aβ plaques, but not on dense-core plaques. Both regimens displayed greater suppression on microgliosis in the cortex than in the hippocampus, and equivalently inhibited astrocytosis in the two brain regions. While both EA and rTMS protected against dendritic degeneration surrounding Aβ plaques, EA further mitigated synaptic loss. These results demonstrated that EA produced more long-lasting and broad-acting effects than rTMS in alleviating memory impairment and pathological products of AD. EA could serve as an early long-term intervention and rTMS as adjuvant therapy in slowing the progression of AD.
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spelling doaj-art-eae06202a84e4d30bb3238fd1aed264f2025-08-20T03:24:26ZengBMCAlzheimer’s Research & Therapy1758-91932025-06-0117111610.1186/s13195-025-01781-zLong-term electroacupuncture and repetitive transcranial magnetic stimulation differentially slow the progression of Alzheimer's disease in App NL−G−F miceSi-Min Song0Qian-Min Liu1Xi Huang2Ping Chen3Min Tao4Xia Pei5Hua-Ning Wang6Yan Han7Jian-Guo Chen8Wei Hong9Zhang-Jin Zhang10Department of Chinese Medicine, the University of Hong Kong-Shenzhen Hospital (HKU-SZH)Shenzhen Key Laboratory of Neuroimmunomodulation for Neurological Diseases, Shenzhen-Hong Kong Institute of Brain Science, Shenzhen Institutes of Advanced Technology, Chinese Academy of SciencesShenzhen Key Laboratory of Neuroimmunomodulation for Neurological Diseases, Shenzhen-Hong Kong Institute of Brain Science, Shenzhen Institutes of Advanced Technology, Chinese Academy of SciencesShenzhen Key Laboratory of Neuroimmunomodulation for Neurological Diseases, Shenzhen-Hong Kong Institute of Brain Science, Shenzhen Institutes of Advanced Technology, Chinese Academy of SciencesShenzhen Key Laboratory of Neuroimmunomodulation for Neurological Diseases, Shenzhen-Hong Kong Institute of Brain Science, Shenzhen Institutes of Advanced Technology, Chinese Academy of SciencesDepartment of Chinese Medicine, the University of Hong Kong-Shenzhen Hospital (HKU-SZH)Department of Psychiatry, Xijing Hospital, the Fourth Military Medical UniversityDepartment of Neurology, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese MedicineDepartment of Pharmacology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and TechnologyShenzhen Key Laboratory of Neuroimmunomodulation for Neurological Diseases, Shenzhen-Hong Kong Institute of Brain Science, Shenzhen Institutes of Advanced Technology, Chinese Academy of SciencesDepartment of Chinese Medicine, the University of Hong Kong-Shenzhen Hospital (HKU-SZH)Abstract Both electroacupuncture (EA) and repetitive transcranial magnetic stimulation (rTMS) possess the potential in combating the progression of Alzheimer’s disease (AD). In this study, we compared the effects of the two regimens as early long-term intervention in App NL−G−F mice, a new amyloid precursor protein (APP) knock-in model that recapitulates multiple AD-associated pathologies, including amyloid-β (Aβ) plaques, microgliosis, astrocytosis, dendritic and synaptic degeneration. The 2-month-old freely moving model mice randomly received EA or rTMS for 2~3 sessions a week for 6 months. Cognitive tests were conducted in Y maze and Barnes maze sequentially at the age of 4, 6, and 8 months. The cortex and hippocampus were dissected thereafter for neurohistological and molecular analysis. Both regimens markedly prevented cognitive deterioration at 6 months old. EA maintained its significant prevention to 8 months old, but rTMS did not. At this age, EA remarkably reduced Aβ burdens with particular dense-core plaques; rTMS had similar effects on Aβ plaques, but not on dense-core plaques. Both regimens displayed greater suppression on microgliosis in the cortex than in the hippocampus, and equivalently inhibited astrocytosis in the two brain regions. While both EA and rTMS protected against dendritic degeneration surrounding Aβ plaques, EA further mitigated synaptic loss. These results demonstrated that EA produced more long-lasting and broad-acting effects than rTMS in alleviating memory impairment and pathological products of AD. EA could serve as an early long-term intervention and rTMS as adjuvant therapy in slowing the progression of AD.https://doi.org/10.1186/s13195-025-01781-zElectroacupunctureTranscranial magnetic stimulationAlzheimer's diseaseApp NL−G−F miceAmyloid plaquesMicrogliosis
spellingShingle Si-Min Song
Qian-Min Liu
Xi Huang
Ping Chen
Min Tao
Xia Pei
Hua-Ning Wang
Yan Han
Jian-Guo Chen
Wei Hong
Zhang-Jin Zhang
Long-term electroacupuncture and repetitive transcranial magnetic stimulation differentially slow the progression of Alzheimer's disease in App NL−G−F mice
Alzheimer’s Research & Therapy
Electroacupuncture
Transcranial magnetic stimulation
Alzheimer's disease
App NL−G−F mice
Amyloid plaques
Microgliosis
title Long-term electroacupuncture and repetitive transcranial magnetic stimulation differentially slow the progression of Alzheimer's disease in App NL−G−F mice
title_full Long-term electroacupuncture and repetitive transcranial magnetic stimulation differentially slow the progression of Alzheimer's disease in App NL−G−F mice
title_fullStr Long-term electroacupuncture and repetitive transcranial magnetic stimulation differentially slow the progression of Alzheimer's disease in App NL−G−F mice
title_full_unstemmed Long-term electroacupuncture and repetitive transcranial magnetic stimulation differentially slow the progression of Alzheimer's disease in App NL−G−F mice
title_short Long-term electroacupuncture and repetitive transcranial magnetic stimulation differentially slow the progression of Alzheimer's disease in App NL−G−F mice
title_sort long term electroacupuncture and repetitive transcranial magnetic stimulation differentially slow the progression of alzheimer s disease in app nl g f mice
topic Electroacupuncture
Transcranial magnetic stimulation
Alzheimer's disease
App NL−G−F mice
Amyloid plaques
Microgliosis
url https://doi.org/10.1186/s13195-025-01781-z
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