High frequency repetitive transcranial magnetic stimulation alleviates cognitive deficits in 3xTg-AD mice by modulating the PI3K/Akt/GLT-1 axis.
High frequency repetitive transcranial magnetic stimulation alleviates cognitive deficits in 3xTg-AD mice by modulating the PI3K/Akt/GLT-1 axis.
复制标题
高频重复经颅磁刺激通过调节PI3K/Akt/GLT-1轴减轻3xTg-AD小鼠的认知缺陷。
DOI：
10.1016/j.redox.2022.102354
复制
发表时间：
2022-08
期刊：
影响因子：
11.4
通讯作者：
Wang, Furong
中科院分区：
文献类型：
--
作者：
Cao, Huan;Zuo, Chengchao;Gu, Zhongya;Huang, Yaqi;Yang, Yuyan;Zhu, Liudi;Jiang, Yongsheng;Wang, Furong
谷氨酸介导的兴奋性毒性，如氧化应激、神经炎症、突触丢失和神经元死亡，在阿尔茨海默病（AD）中普遍存在。我们以前的研究发现，15 Hz重复经颅磁刺激（rTMS）可以降低皮层兴奋性。本研究旨在探讨高频rTMS对3xTg-AD模型小鼠的治疗作用，并进一步探讨rTMS的作用机制。首先，WT和3xTg-AD模型小鼠接受25 Hz rTMS治疗21天。采用Morris水迷宫实验评价大鼠的认知功能。采用ELISA和免疫荧光法检测Aβ水平和神经炎症反应。通过生化测定试剂盒定量氧化应激。采用18F-FDG PET评价脑葡萄糖代谢。Western blot和TUNEL染色检测细胞凋亡。Western blot检测突触可塑性和PI 3 K/Akt/GLT-1通路相关蛋白表达。接下来，为探讨PI 3 K/Akt活性在rTMS治疗中的作用，对3xTg-AD模型小鼠给予LY 294002干预和rTMS治疗21 d，实验方法同前。结果表明，25 Hz rTMS能改善3xTg-AD模型小鼠的认知功能，降低海马Aβ1-42水平，改善氧化应激，改善糖代谢。rTMS可减轻神经炎性反应，增强突触可塑性，减少神经元丢失和细胞凋亡，并伴有PI 3 K/Akt/GLT-1通路的激活。给予PI 3 K/Akt抑制剂LY 294002后，25 Hz rTMS不能改善3xTg-AD模型小鼠的认知功能和减轻神经元损伤，也不能上调GLT-1的表达，提示其治疗和保护作用需要PI 3 K/Akt/GLT-1通路的参与。rTMS通过调节多种病理过程对AD发挥保护作用。同时，本研究揭示了PI 3 K/Akt/GLT-1通路在rTMS治疗AD中的关键作用，可能成为rTMS治疗AD的新靶点。
Glutamate mediated excitotoxicity, such as oxidative stress, neuroinflammation, synaptic loss and neuronal death, is ubiquitous in Alzheimer's disease (AD). Our previous study found that 15 Hz repetitive transcranial magnetic stimulation (rTMS) could reduce cortical excitability. The purpose of this study was to explore the therapeutic effect of higher frequency rTMS on 3xTg-AD model mice and further explore the mechanisms of rTMS. First, WT and 3xTg-AD model mice received 25 Hz rTMS treatment for 21 days. The Morris water maze test was used to evaluate the cognitive function. The levels of Aβ and neuroinflammation were assessed by ELISA and immunofluorescence. Oxidative stress was quantified by biochemical assay kits. Brain glucose metabolism was assessed by 18F-FDG PET. Apoptosis was assessed by western blot and TUNEL staining. Synaptic plasticity and PI3K/Akt/GLT-1 pathway related protein expression were assessed by western blot. Next, to explore the activity of PI3K/Akt in the therapeutic effect of rTMS, 3xTg-AD model mice were given LY294002 intervention and rTMS treatment for 21 days, the experimental method was the same as before. We found that 25 Hz rTMS could improve cognitive function of 3xTg-AD model mice, reduce hippocampal Aβ1-42 levels, ameliorate oxidative stress and improve glucose metabolism. rTMS alleviated neuroinflammatory response, enhanced synaptic plasticity and reduced neuronal loss and cell apoptosis, accompanied by activation of PI3K/Akt/GLT-1 pathway. After administration of PI3K/Akt inhibitor LY294002, 25 Hz rTMS could not improve the cognitive function and reduce neuron damage of 3xTg-AD model mice, nor could it upregulate the expression of GLT-1, indicating that its therapeutic and protective effects required the involvement of PI3K/Akt/GLT-1 pathway. rTMS exerts protective role for AD through regulating multiple pathological processes. Meanwhile, this study revealed the key role of PI3K/Akt/GLT-1 pathway in the treatment of AD by rTMS, which might be a new target.
登录
查看更多内容
加兰他敏改善小鼠认知、海马炎症和脂多糖引起的突触可塑性损伤
影响因子：
9.3
作者：
Liu Y;Zhang Y;Zheng X;Fang T;Yang X;Luo X;Guo A;Newell KA;Huang XF;Yu Y
通讯作者：
Yu Y
影响因子：
6.2
作者：
Kreisel, Tirzah;Wolf, Brachi;Licht, Tamar
通讯作者：
Licht, Tamar
早期干预可减轻 5xFAD 小鼠的突触可塑性损伤和神经炎症
影响因子：
4.8
作者：
Li, Kai;Wang, Xin;Yang, Zhuo
通讯作者：
Yang, Zhuo
影响因子：
2.7
作者：
Ikeda T;Kobayashi S;Morimoto C
通讯作者：
Morimoto C
影响因子：
11.4
作者：
Cheignon C;Tomas M;Bonnefont-Rousselot D;Faller P;Hureau C;Collin F
通讯作者：
Collin F