The effect and mechanism of patchouli alcohol on cognitive dysfunction in AD mice induced by Aβ1–42 oligomers through AMPK/mTOR pathway

IF 3.5 3区医学 Q2 NEUROSCIENCES

Brain Research Bulletin Pub Date : 2024-07-10 DOI:10.1016/j.brainresbull.2024.111030

Li-Ting Lin , Shu-Ting Zhang , Bao-Ling Shang , Yu-Qiong Dai , Xiao-Qing Cheng , Qing-Guang Wu , Ruo-Ting Zhan , Si-Jun Liu

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引用次数: 0

Abstract

Alzheimer's disease (AD) is a neurodegenerative brain disorder that progressively impairs long-term and working memory. The function and mechanism of PA(Patchouli alcohol) in improving AD in the external treatment of encephalopathy remain unclear. This study aimed to investigate the therapeutic effect of PA on AD using an Aβ_1–42 induced AD mouse model with LPS(Lipopolysaccharide) stimulation of BV2 microglial cells. Additionally, we aimed to explore the potential mechanism of PA in enhancing autophagy and reducing neuroinflammation through the AMPK (AMP-activated protein kinase)/mTOR (Mammaliam target of rapamycin) signaling pathway. The Morris water maze was used to assess cognitive function, and cortical and hippocampal tissues were collected for further analysis of the corresponding signaling pathways and inflammatory changes through biological experiments. Our research findings demonstrate that PA has a significant positive impact on cognitive and memory impairments in mice that have been induced with Aβ_1–42-induced AD. Additionally, PA was also found to revert the activation of microglia induced by LPS. These effects may be attributed to the reduction of neuroinflammation and enhancement of the AMPK/mTOR autophagy pathway. Therefore, PA may serve as an effective therapeutic option to prevent or delay the progression of AD-associated memory dysfunction.

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藿香醇通过AMPK/mTOR途径对Aβ1-42寡聚体诱导的AD小鼠认知功能障碍的影响及机制

阿尔茨海默病（AD）是一种神经退行性脑病，会逐渐损害长期记忆和工作记忆。在脑病的外部治疗中，PA（广藿香醇）改善 AD 的功能和机制仍不清楚。本研究旨在利用Aβ1-42诱导的AD小鼠模型，通过LPS（脂多糖）刺激BV2小胶质细胞，研究PA对AD的治疗效果。此外，我们还旨在探索 PA 通过 AMPK（AMP 激活蛋白激酶）/mTOR（雷帕霉素靶蛋白）信号通路增强自噬和减轻神经炎症的潜在机制。研究人员利用莫里斯水迷宫评估认知功能，并收集大脑皮层和海马组织，通过生物实验进一步分析相应的信号通路和炎症变化。我们的研究结果表明，PA对Aβ1-42诱导的AD小鼠的认知和记忆损伤有显著的积极影响。此外，我们还发现 PA 能逆转 LPS 诱导的小胶质细胞激活。这些作用可能归因于神经炎症的减少和 AMPK/mTOR 自噬途径的增强。因此，PA 可以作为一种有效的治疗选择，预防或延缓与 AD 相关的记忆功能障碍的发展。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Brain Research Bulletin 医学-神经科学

CiteScore

6.90

自引率

2.60%

发文量

253

审稿时长

67 days

期刊介绍： The Brain Research Bulletin (BRB) aims to publish novel work that advances our knowledge of molecular and cellular mechanisms that underlie neural network properties associated with behavior, cognition and other brain functions during neurodevelopment and in the adult. Although clinical research is out of the Journal''s scope, the BRB also aims to publish translation research that provides insight into biological mechanisms and processes associated with neurodegeneration mechanisms, neurological diseases and neuropsychiatric disorders. The Journal is especially interested in research using novel methodologies, such as optogenetics, multielectrode array recordings and life imaging in wild-type and genetically-modified animal models, with the goal to advance our understanding of how neurons, glia and networks function in vivo.