Early intervention attenuates synaptic plasticity impairment and neuroinflammation in 5xFAD mice
Early intervention attenuates synaptic plasticity impairment and neuroinflammation in 5xFAD mice
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早期干预可减轻 5xFAD 小鼠的突触可塑性损伤和神经炎症
DOI：
10.1016/j.jpsychires.2021.02.007
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发表时间：
2021-02-19
影响因子：
4.8
通讯作者：
Yang, Zhuo
中科院分区：
文献类型：
--
作者：
Li, Kai;Wang, Xin;Yang, Zhuo
背景：随着老年痴呆症人口的增加？阿尔茨海默病（AD）患者逐年增加，严重威胁着人类健康，迫切需要有效的预防和治疗方法。生物标志物变化与？淀粉样蛋白(?)因此早期干预是AD治疗的一个可行的思路。重复经颅磁刺激（rTMS）作为一种非侵入性技术提供了早期干预的可能性。目的：探讨高频rTMS对AD转基因小鼠病理症状的影响及其机制，在小鼠头部上方2mm处放置8字线圈，连续14天施加20 Hz高强度rTMS。方法：采用体内电生理记录、行为学测试、免疫印迹法和免疫荧光法检测AD的病理症状。结果：我们的数据显示，早期干预可有效降低A？水平和小胶质细胞的激活，以及促炎细胞因子，包括IL-6和TNF-？以及调节的PI3K/Akt/NF-？另一方面，B信号通路，这创造了一个有利的大脑环境。由此可见，它增加了早期5xFAD转基因小鼠脑内突触相关蛋白的表达，改善了神经元突触的可塑性。结论：本研究首次提出20hz rTMS早期干预可通过PI3K/Akt/NF-?改善5xFAD小鼠早期神经炎症，改善突触可塑性。B信号通路。
Background: As an increasing population of Alzheimer?s disease (AD) patients year by year, which is a serious threat to human health, an effective approach to prevent and treat AD is required. Biomarker changes relevant to ?-amyloid (A?) 20 years or more in advance of cognitive impairment, so early intervention is a feasible idea for AD therapy. Repetitive transcranial magnetic stimulation (rTMS) as a non-invasive technique offers the possibility of early intervention.Objective: To explore the effect of high-frequency rTMS on the pathological symptoms of AD transgenic mice and its mechanisms, a figure-of-eight coil was placed 2 mm above the head of mouse to apply 20 Hz high-intensity rTMS for 14 consecutive days.Methods: In vivo electrophysiological recording, behavioral test, Western blots assay and immunofluorescence were used to measure the pathological symptoms of AD.Results: Our data showed that early intervention effectively reduced A? levels and the activation of microglia on the one hand, and decreased levels of pro-inflammatory cytokines including IL-6 and TNF-? as well as regulated PI3K/Akt/NF-?B signaling pathway on the other hand, which created a favorable brain environment. Thus, it increased the expression of synapse-associated proteins and improved neuronal synaptic plasticity in brain of early-stage of 5xFAD transgenic mice.Conclusions: This study is the first to suggest that early intervention of 20 Hz rTMS ameliorates neuroinflammation to improve synaptic plasticity of early-stage of 5xFAD mice through PI3K/Akt/NF-?B signaling pathway.