Rotating magnetic field improves cognitive and memory impairments in APP/PS1 mice by activating autophagy and inhibiting the PI3K/AKT/mTOR signaling pathway

IF 4.6 2区医学 Q1 NEUROSCIENCES

Experimental Neurology Pub Date : 2024-10-25 DOI:10.1016/j.expneurol.2024.115029

Mengqing Li , Yaxian Mo , Qinyao Yu , Umer Anayyat , Hua Yang , Fen Zhang , Yunpeng Wei , Xiaomei Wang

{"title":"Rotating magnetic field improves cognitive and memory impairments in APP/PS1 mice by activating autophagy and inhibiting the PI3K/AKT/mTOR signaling pathway","authors":"Mengqing Li , Yaxian Mo , Qinyao Yu , Umer Anayyat , Hua Yang , Fen Zhang , Yunpeng Wei , Xiaomei Wang","doi":"10.1016/j.expneurol.2024.115029","DOIUrl":null,"url":null,"abstract":"<div><div>Alzheimer's disease (AD) is a geriatric disorder that can be roughly classified into sporadic AD and hereditary AD. The latter is strongly associated with genetic factors, and its treatment poses greater challenges compared to sporadic AD. Rotating magnetic fields (RMF) is a non-invasive treatment known to have diverse biological effects, including the modulation of the central nervous system and aging. However, the impact of RMF on hereditary AD and its underlying mechanism remain unexplored. In this study, we exposed APP/PS1 mice to RMF (2 h/day, 0.2 T, 4 Hz) for a duration of 6 months. The results demonstrated that RMF treatment significantly ameliorated their cognitive and memory impairments, attenuated neuronal damage, and reduced amyloid deposition. Furthermore, RNA-sequencing analysis revealed a significant enrichment of autophagy-related genes and the PI3K/AKT-mTOR signaling pathway. Western blotting further confirmed that RMF activated autophagy and suppressed the phosphorylation of proteins associated with the PI3K/AKT/mTOR signaling pathway in APP/PS1 mice. These protective effects and the underlying mechanism were also observed in Aβ<sub>25</sub><sub>–</sub><sub>35</sub>-exposed HT22 cells. Collectively, our findings indicate that RMF improves cognitive and memory dysfunction in APP/PS1 mice by activating autophagy and inhibiting the PI3K/AKT/mTOR signaling pathway, thus highlighting the potential of RMF as a clinical treatment for hereditary AD.</div></div>","PeriodicalId":12246,"journal":{"name":"Experimental Neurology","volume":"383 ","pages":"Article 115029"},"PeriodicalIF":4.6000,"publicationDate":"2024-10-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Experimental Neurology","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0014488624003558","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"NEUROSCIENCES","Score":null,"Total":0}

引用次数: 0

Abstract

Alzheimer's disease (AD) is a geriatric disorder that can be roughly classified into sporadic AD and hereditary AD. The latter is strongly associated with genetic factors, and its treatment poses greater challenges compared to sporadic AD. Rotating magnetic fields (RMF) is a non-invasive treatment known to have diverse biological effects, including the modulation of the central nervous system and aging. However, the impact of RMF on hereditary AD and its underlying mechanism remain unexplored. In this study, we exposed APP/PS1 mice to RMF (2 h/day, 0.2 T, 4 Hz) for a duration of 6 months. The results demonstrated that RMF treatment significantly ameliorated their cognitive and memory impairments, attenuated neuronal damage, and reduced amyloid deposition. Furthermore, RNA-sequencing analysis revealed a significant enrichment of autophagy-related genes and the PI3K/AKT-mTOR signaling pathway. Western blotting further confirmed that RMF activated autophagy and suppressed the phosphorylation of proteins associated with the PI3K/AKT/mTOR signaling pathway in APP/PS1 mice. These protective effects and the underlying mechanism were also observed in Aβ₂₅_–₃₅-exposed HT22 cells. Collectively, our findings indicate that RMF improves cognitive and memory dysfunction in APP/PS1 mice by activating autophagy and inhibiting the PI3K/AKT/mTOR signaling pathway, thus highlighting the potential of RMF as a clinical treatment for hereditary AD.

查看原文本刊更多论文

旋转磁场通过激活自噬和抑制 PI3K/AKT/mTOR 信号通路，改善 APP/PS1 小鼠的认知和记忆障碍。

阿尔茨海默病（AD）是一种老年性疾病，大致可分为散发性阿尔茨海默病和遗传性阿尔茨海默病。遗传性阿尔茨海默病与遗传因素密切相关，与散发性阿尔茨海默病相比，遗传性阿尔茨海默病的治疗面临更大的挑战。众所周知，旋转磁场（RMF）是一种非侵入性治疗方法，具有多种生物效应，包括调节中枢神经系统和衰老。然而，RMF 对遗传性 AD 的影响及其内在机制仍有待探索。在本研究中，我们将 APP/PS1 小鼠暴露于 RMF（2 小时/天，0.2 T，4 Hz），为期 6 个月。结果表明，RMF 治疗显著改善了小鼠的认知和记忆障碍，减轻了神经元损伤，减少了淀粉样蛋白沉积。此外，RNA序列分析显示，自噬相关基因和PI3K/AKT-mTOR信号通路显著富集。Western blotting进一步证实，在APP/PS1小鼠体内，RMF激活了自噬，并抑制了与PI3K/AKT/mTOR信号通路相关的蛋白质磷酸化。在暴露于Aβ25-35的HT22细胞中也观察到了这些保护作用及其机制。总之，我们的研究结果表明，RMF能通过激活自噬和抑制PI3K/AKT/mTOR信号通路来改善APP/PS1小鼠的认知和记忆功能障碍，从而凸显了RMF作为遗传性AD临床治疗方法的潜力。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊

Experimental Neurology 医学-神经科学

CiteScore

10.10

自引率

3.80%

发文量

258

审稿时长

42 days

期刊介绍： Experimental Neurology, a Journal of Neuroscience Research, publishes original research in neuroscience with a particular emphasis on novel findings in neural development, regeneration, plasticity and transplantation. The journal has focused on research concerning basic mechanisms underlying neurological disorders.