Effect of transcranial magnetic stimulation on potassium channels in the dentate gyrus of the hippocampus of Alzheimer’s disease mice

doi:10.12307/2025.379

Abstract

Abstract: BACKGROUND: Transcranial magnetic stimulation has been used in the treatment of Alzheimer’s disease, but its mechanism has not been fully clarified.
OBJECTIVE: To explore the mechanism of repetitive transcranial magnetic stimulation to increase neural excitability in mice with Alzheimer’s disease.
METHODS: Sixteen C57BL/6 mice were randomized into control group (n=8) and control+magnetic stimulation group (n=8). Another 16 APP/PS1 mice were randomized into dementia group (n=8) and dementia+magnetic stimulation group (n=8). Mice in the two magnetic stimulation groups were given repetitive transcranial magnetic stimulation, 2 hours daily, for 14 continuous days. The water maze was then used to detect the cognitive function of mice. Whole-cell membrane-clamp technique was used to collect action potentials and analyze the effect of Alzheimer’s disease on action potentials; and the potassium channel currents were collected and analyzed for the role of their kinetic properties on neural excitability.
RESULTS AND CONCLUSION: The results of Morris water maze showed that normal mice could find and determine the original platform more accurately after receiving repetitive transcranial magnetic stimulation, while Alzheimer’s disease led to a decrease in the learning and memory ability of mice, a decrease in the number of times they found the platform, and a degeneration of neurons in the hippocampal dentate gyrus. Repetitive transcranial magnetic stimulation could improve the learning and memory ability of mice with Alzheimer’s disease. Whole-cell membrane clamp technique assay showed that repetitive transcranial magnetic stimulation could trigger neuronal depolarization and enhance neuronal excitability in Alzheimer’s disease mice. Analysis of potassium channel currents showed that Alzheimer’s disease caused an increase in the transient outward potassium channel half-activation voltage. The inactivation curve was shifted in the direction of depolarization and the resuscitation time constant was prolonged, causing the delayed rectifier potassium channel activation curve to be shifted in the direction of depolarization. Whereas repetitive transcranial magnetic stimulation delayed the opening and closing of the potassium channel and inhibit the efflux of intracellular potassium ions, which resulted in the retention of a higher intracellular potassium concentration and increased neuronal excitability. To conclude, repetitive transcranial magnetic stimulation may alleviate cognitive decline by increasing neuronal excitability in the hippocampal dentate gyrus.

中国组织工程研究杂志出版内容重点：组织构建；骨细胞；软骨细胞；细胞培养；成纤维细胞；血管内皮细胞；骨质疏松；组织工程

Key words: repetitive transcranial magnetic stimulation, whole-cell membrane clamp, K+ channels, water maze, neuronal excitability, learning memory, action potential

CLC Number:

Qian Lei, Yu Hongli, Zhao Xiuzhi, Zhu Yucan. Effect of transcranial magnetic stimulation on potassium channels in the dentate gyrus of the hippocampus of Alzheimer’s disease mice[J]. Chinese Journal of Tissue Engineering Research, 2025, 29(12): 2544-2552.

Figures/Tables 10

单个动作电位的阈值、达峰时间、峰值、最大上升斜率、后超极化电位、半波宽等指标见图7所示。由图7a可知，基因对动作电位阈值产生了显著影响[F(1，22)=7.371，P < 0.05]，刺激对小鼠动作电位阈值产生了显著影响[F(1，22)=22.336，P < 0.001]。组间比较结果显示，痴呆组小鼠阈值显著高于对照组(P < 0.01)，痴呆+磁刺激组阈值显著低于痴呆组(P < 0.01)，对照+磁刺激组阈值显著低于对照组(P < 0.001)。由图7b可知，基因对动作电位达峰时间产生了显著影响[F(1，22)=4.308，P < 0.05]，刺激对小鼠动作电位达峰时间没有产生显著影响[F(1，22)=0.016，P > 0.05]。组间比较结果显示，痴呆组小鼠达峰时间显著低于对照组(P < 0.05)，痴呆+磁刺激组达峰时间与痴呆组比较差异无显著性意义(P > 0.05)。由图7c可知，基因对动作电位峰值没有产生显著影响[F(1，22)=0.672，P > 0.05]，刺激对小鼠动作电位峰值没有产生显著影响[F(1，22)=3.907，P > 0.05]。经组间分析结果显示，痴呆组小鼠峰值显著低于对照组(P < 0.001)，痴呆+磁刺激组峰值显著高于痴呆组(P < 0.05)。由图7d可知，基因对动作电位最大上升速率产生了显著影响[F(1，22)=113.797，P < 0.001]，刺激对小鼠动作电位最大上升速率产生了显著影响[F(1，22)=174.166，P < 0.001]。组间比较结果现实，痴呆组小鼠最大上升速率显著低于对照组(P < 0.01)，痴呆+磁刺激组最大上升速率显著高于痴呆组(P < 0.01)。由图7e可知，基因对动作电位后超极化电位没有产生显著影响[F(1，22)=3.103，P > 0.05]，刺激对小鼠动作电位后超极化电位产生了显著影响[F(1，22)=49.655，P < 0.001]。组间比较结果显示，痴呆组小鼠后超极化电位显著高于对照组(P < 0.001)，痴呆+磁刺激组后超极化电位显著低于痴呆组(P < 0.001)。由图7f可知，基因对动作电位半波宽产生了显著影响[F(1，22)=11.088，P < 0.01]，刺激对小鼠动作电位半波宽产生了显著影响[F(1，22)=7.801，P < 0.05]。组间比较结果显示，痴呆组小鼠半波宽显著短于对照组(P < 0.01)，痴呆+磁刺激组半波宽与痴呆组比较差异无显著性意义(P > 0.05)。"

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