Pang Yongfeng, Shi Mingfei
Department of Rehabilitation, Tiantai People's Hospital of Zhejiang Province, Zhengjiang, 317200, People's Republic of China.
Neuropsychiatr Dis Treat. 2021 Jul 2;17:2151-2161. doi: 10.2147/NDT.S311183. eCollection 2021.
Mild cognitive impairment (MCI) is a typical symptom of early Alzheimer's disease (AD) and is driven by the dysfunction of microRNAs (miRs). Repetitive transcranial magnetic stimulation (rTMS) is a non-invasive technique for handling neuropsychiatric disorders and has universally effects on the functions of miRs. In the current study, the improvement effects of rTMS on MCI associated with AD were explored by focusing on miR-567/NEUROD2/PSD95 axis.
MCI was induced in mice using scopolamine and was treated with rTMS of two frequencies (1 Hz and 10 Hz). The changes in cognitive function, brain structure, neurotrophic factor levels, and activity of miR-567/NEUROD2/PSD95 axis were assessed. The interaction between rTMS and miR-567 was further verified by inducing the level of miR-567 in AD mice.
The administrations of rTMS improved the cognitive function of AD mice and attenuated brain tissue destruction, which were associated with the restored production of BDNF and NGF. Additionally, rTMS administrations suppressed the expression of miR-567 and up-regulated the expressions of NEUROD2 and PSD95, which contributed to the improved condition in central nerve system. With the induced level of miR-567, the effects of rTMS were counteracted: the learning and memorizing abilities of mice were impaired, the brain neuron viability was suppressed, and the production of neurotrophic factors was suppressed even under the administration of rTMS. The changes in brain function and tissues were associated with the inhibited expressions of NEUROD2 and PSD95.
The findings outlined in the current study demonstrated that rTMS treatment could protect brain against AD-induced MCI without significant side effects, and the function depended on the inhibition of miR-567.
轻度认知障碍（MCI）是早期阿尔茨海默病（AD）的典型症状，由微小RNA（miR）功能障碍所致。重复经颅磁刺激（rTMS）是一种治疗神经精神疾病的非侵入性技术，对miR的功能具有广泛影响。在本研究中，通过聚焦miR-567/NEUROD2/PSD95轴，探讨rTMS对AD相关MCI的改善作用。
使用东莨菪碱诱导小鼠出现MCI，并对其进行两种频率（1Hz和10Hz）的rTMS治疗。评估认知功能、脑结构、神经营养因子水平以及miR-567/NEUROD2/PSD95轴活性的变化。通过诱导AD小鼠体内miR-567水平，进一步验证rTMS与miR-567之间的相互作用。
rTMS治疗改善了AD小鼠的认知功能，减轻了脑组织破坏，这与脑源性神经营养因子（BDNF）和神经生长因子（NGF）的恢复产生有关。此外，rTMS治疗抑制了miR-567的表达，上调了NEUROD2和PSD95的表达，这有助于改善中枢神经系统状况。随着miR-567水平的诱导，rTMS的作用被抵消：即使在rTMS治疗下，小鼠的学习和记忆能力受损，脑神经元活力受到抑制，神经营养因子的产生也受到抑制。脑功能和组织的变化与NEUROD2和PSD95表达的抑制有关。
本研究结果表明，rTMS治疗可保护大脑免受AD诱导的MCI影响，且无明显副作用，其功能依赖于对miR-567的抑制。
