Repetitive Transcranial Magnetic Stimulation Ameliorates Cognitive Dysfunction in Alzheimer’s Disease Mice by Inhibiting Ferroptosis and Maintaining Cytoplasmic Calcium Homeostasis
10.16476/j.pibb.2025.0023CSTR：32369.14.pibb.20250023
- VernacularTitle:重复经颅磁刺激通过影响神经元铁死亡和钙稳态改善阿尔茨海默病小鼠认知功能
- Author:
Meng ZHANG
1
;
Ze ZHANG
1
;
Rui FU
1
;
Zi-Hao REN
1
;
Chong DING
1
Author Information
1. College of Health Sciences & Biomedical Engineering, Hebei University of Technology, Tianjin 300130, China
- Publication Type:Journal Article
- Keywords:
Alzheimer’s disease;
repetitive transcranial magnetic stimulation;
ferroptosis;
calcium homeostasis;
cognitive function
- From:
Progress in Biochemistry and Biophysics
2025;52(8):2117-2130
- CountryChina
- Language:Chinese
-
Abstract:
ObjectiveRepetitive transcranial magnetic stimulation (rTMS), a non-invasive brain stimulation technique, offers a non-pharmacological therapeutic option for the management of Alzheimer’s disease (AD). Studies have demonstrated that ferroptosis plays a pivotal role in the pathological onset and progression of AD, and the inhibition of neuronal ferroptosis can significantly ameliorate cognitive impairments associated with AD. The imbalance of calcium ion (Ca2+) homeostasis is intimately associated with the pathology of AD and serves as a catalyst for the induction of ferroptosis through various pathways. This study is designed to investigate whether rTMS can ameliorate AD by inhibiting neuronal ferroptosis or maintaining calcium homeostasis, ultimately establishing a theoretical and experimental framework for the utilization of rTMS in AD treatment. MethodsAPP/PS1 AD mice were subjected to both 0.5 Hz low-frequency and 20 Hz high-frequency rTMS treatments, and the efficacy of these treatments was evaluated using novel object recognition and Morris water maze tests. ELISA was employed to quantify the levels of glutathione (GSH), malondialdehyde (MDA), superoxide dismutase (SOD), Fe2+ within the hippocampi of mice from each group. HT-22 cells were induced to undergo ferroptosis via Erastin treatment, and subsequent to high- and low-frequency magnetic stimulation, cell viability was assessed using CCK-8 assay, while intracellular calcium ion concentration fluctuations were monitored using Fluo-4 AM. ResultsThe findings revealed that, when compared to normal mice, AD mice displayed a notable decline in cognitive function, accompanied by a substantial increase in ferroptosis levels and intracellular calcium ion concentrations. Both high-frequency and low-frequency applications of rTMS were found to significantly ameliorate cognitive impairments in AD mice, while also effectively mitigating the abnormal augmentation of neuronal ferroptosis and intracellular calcium ion levels. ConclusionThe present study underscores that both high-frequency and low-frequency rTMS exhibit efficacy in alleviating cognitive dysfunction in AD mice, potentially through the modulation of ferroptosis and intracellular calcium ion homeostasis.
