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在淀粉样蛋白诱导的阿尔茨海默病小鼠模型中,电针通过PI3K/Akt信号通路减轻学习和记忆障碍。

Electroacupuncture Attenuates Learning and Memory Impairment via PI3K/Akt Pathway in an Amyloid -Induced Alzheimer's Disease Mouse Model.

作者信息

Shao Si-Mai, Park Kyung Hye, Yuan Ye, Zhang Zijuan, You Yanwen, Zhang Zhenqiang, Hao Li

机构信息

Medical College, Henan University of Chinese Medicine, Zhengzhou, China.

Academy of Chinese Medical Sciences, Henan University of Chinese Medicine, Zhengzhou, China.

出版信息

Evid Based Complement Alternat Med. 2022 Apr 15;2022:3849441. doi: 10.1155/2022/3849441. eCollection 2022.

Abstract

The main characteristic of Alzheimer's disease (AD) is the progressive decline of learning and memory ability. Electroacupuncture (EA) may improve AD-related learning and memory ability. However, the underlying molecular mechanism of action remains unclear. The objective of the present study was to assess the effects and the molecular mechanism of EA on learning and memory in an amyloid (A ) induced AD mouse model. The AD model was established by intracerebroventricular (ICV) administration of A oligomers. AD mice were electroacupunctured with wisdom three-needle combined with Baihui (GV20) five times per week for three consecutive weeks. The Morris water maze (MWM) and Y maze tests were applied to evaluate spatial learning and memory ability. A transmission electron microscope (TEM) was used to measure mitochondria and autophagy of hippocampal neurons, and western blot was applied to observe molecular changes in the mice hippocampus. The results suggested that EA treatment significantly alleviated learning and memory impairment related to AD, reduced mitochondria damage, improved autophagy, increased mitochondrial protein 2 (Mfn2), Beclin 1, and LC3B, and decreased the expressions of fission protein 1 (Fis1) level. Furthermore, EA further upregulated the protein expression of phosphatidylinositol 3-kinase (PI3K) and the ratio of p-Akt/Akt in the hippocampus of AD mice. This study demonstrates that EA treatment attenuates cognitive deficits, modulates mitochondrial fusion and fission, and enhances autophagy via the PI3K/Akt pathway in a mouse AD model.

摘要

阿尔茨海默病(AD)的主要特征是学习和记忆能力的渐进性衰退。电针(EA)可能改善与AD相关的学习和记忆能力。然而,其潜在的分子作用机制仍不清楚。本研究的目的是评估EA对淀粉样蛋白(Aβ)诱导的AD小鼠模型学习和记忆的影响及其分子机制。通过脑室内(ICV)注射Aβ寡聚体建立AD模型。AD小鼠每周接受5次智三针结合百会(GV20)电针治疗,连续治疗3周。采用莫里斯水迷宫(MWM)和Y迷宫试验评估空间学习和记忆能力。使用透射电子显微镜(TEM)测量海马神经元的线粒体和自噬情况,并应用蛋白质印迹法观察小鼠海马中的分子变化。结果表明,EA治疗显著减轻了与AD相关的学习和记忆障碍,减少了线粒体损伤,改善了自噬,增加了线粒体蛋白2(Mfn2)、Beclin 1和LC3B的表达,并降低了裂变蛋白1(Fis1)的表达水平。此外,EA进一步上调了AD小鼠海马中磷脂酰肌醇3激酶(PI3K)的蛋白表达以及p-Akt/Akt的比值。本研究表明,在小鼠AD模型中,EA治疗通过PI3K/Akt途径减轻认知缺陷,调节线粒体融合和裂变,并增强自噬。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/84cd/9033336/e547bc27db33/ECAM2022-3849441.001.jpg

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