Wu Qi, Xu Xingjun, Zhai Chenyuan, Zhao Zhiyong, Dai Wenjun, Wang Tong, Shen Ying
Rehabilitation Medicine Center, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
Department of Rehabilitation, Hengyang Medical School, The First Affiliated Hospital, University of South China, Hengyang, China.
Front Neurosci. 2022 Aug 5;16:974940. doi: 10.3389/fnins.2022.974940. eCollection 2022.
BACKGROUND: Repetitive 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. METHODS: A total of 30 healthy adult rats were randomly divided into the control group and the rTMS group ( = 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. RESULTS: After 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 -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. CONCLUSION: Overall, these data suggested that HF-rTMS can enhance cognitive performance through modulation of NMDA receptor-dependent brain plasticity.
背景：重复经颅磁刺激（rTMS）是刺激结构和功能可塑性变化的一种有效方法，而结构和功能可塑性变化是学习和记忆的一部分。然而，据我们所知，rTMS在影响认知的不同脑区所诱导的特定活动和神经可塑性尚未完全明确，其机制也不清楚。因此，我们旨在研究rTMS在不同脑区诱导的与认知相关的神经可塑性变化及其机制。 方法：总共30只健康成年大鼠被随机分为对照组和rTMS组（每组15只大鼠）。对照组和rTMS组的大鼠分别在额叶前皮质（PFC）接受4周的假刺激或高频rTMS（HF-rTMS）。通过莫里斯水迷宫检测认知功能。在rTMS前后通过静息态功能磁共振成像（rs-fMRI）进行功能成像。rTMS后，通过蛋白质免疫印迹法检测PFC、海马体和初级运动皮质（M1）中脑源性神经营养因子（BDNF）、酪氨酸激酶受体B（TrkB）、磷酸化蛋白激酶B（p-Akt）、蛋白激酶B（Akt）、N-甲基-D-天冬氨酸（NMDA）受体1（NR1）、NMDA受体2A（NR2A）和NMDA受体2B（NR2B）的蛋白表达。 结果：rTMS治疗4周后，接受rTMS的健康大鼠在空间情景学习和记忆表现方面的认知能力有小幅但显著的行为改善。与rTMS前或对照组相比，rTMS组大鼠在内感受/默认模式网络（DMN）和皮质-纹状体-丘脑网络的多个脑区，特别是双侧PFC、双侧海马体和左侧M1的局部一致性（ReHo）增加。蛋白质免疫印迹分析表明，rTMS导致PFC、海马体和M1中NMDA受体（包括NR1、NR2A和NR2B）的表达显著增加，以及这三个脑区中BDNF、TrkB和p-Akt的上调。此外，这三个脑区中NR1的表达与rTMS诱导的认知改善相关。 结论：总体而言，这些数据表明HF-rTMS可通过调节NMDA受体依赖性脑可塑性来增强认知表现。
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