High-frequency repetitive transcranial magnetic stimulation improves spatial episodic learning and memory performance by regulating brain plasticity in healthy rats

Author:

Wu Qi,Xu Xingjun,Zhai Chenyuan,Zhao Zhiyong,Dai Wenjun,Wang Tong,Shen Ying

Abstract

BackgroundRepetitive transcranial magnetic stimulation (rTMS) is an effective way to stimulate changes in structural and functional plasticity, which is a part of learning and memory. However, to our knowledge, rTMS-induced specific activity and neural plasticity in different brain regions that affect cognition are not fully understood; nor are its mechanisms. Therefore, we aimed to investigate rTMS-induced cognition-related neural plasticity changes and their mechanisms in different brain regions.MethodsA total of 30 healthy adult rats were randomly divided into the control group and the rTMS group (n = 15 rats per group). The rats in the control and the rTMS group received either 4 weeks of sham or high-frequency rTMS (HF-rTMS) over the prefrontal cortex (PFC). Cognitive function was detected by Morris water maze. Functional imaging was acquired by resting-state functional magnetic resonance imaging (rs-fMRI) before and after rTMS. The protein expressions of BDNF, TrkB, p-Akt, Akt, NR1, NR2A, and NR2B in the PFC, hippocampus, and primary motor cortex (M1) were detected by Western blot following rTMS.ResultsAfter 4 weeks of rTMS, the cognitive ability of healthy rats who underwent rTMS showed a small but significant behavioral improvement in spatial episodic learning and memory performance. Compared with the pre-rTMS or the control group, rats in the rTMS group showed increased regional homogeneity (ReHo) in multiple brain regions in the interoceptive/default mode network (DMN) and cortico-striatal-thalamic network, specifically the bilateral PFC, bilateral hippocampus, and the left M1. Western blot analyses showed that rTMS led to a significant increase in the expressions of N-methyl-D-aspartic acid (NMDA) receptors, including NR1, NR2A, and NR2B in the PFC, hippocampus, and M1, as well as an upregulation of BDNF, TrkB, and p-Akt in these three brain regions. In addition, the expression of NR1 in these three brain regions correlated with rTMS-induced cognitive improvement.ConclusionOverall, these data suggested that HF-rTMS can enhance cognitive performance through modulation of NMDA receptor-dependent brain plasticity.

Funder

National Key Research and Development Program of China

Medical Science and Technology Development Foundation, Nanjing Municipality Health Bureau

Publisher

Frontiers Media SA

Subject

General Neuroscience

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