肠道微生物组通过PI3K/Akt信号传递对6PPD-奎诺因引起的认知障碍作出贡献
1GCP Office, The Affiliated Brain Hospital of Nanjing Medical University, Nanjing 210029, China.
Toxicology
|June 12, 2025
概括
暴露于N-(1,3-二甲基) -N'--p-phenylenediamine-quinone (6PPD-Q) 的物质会影响认知功能和记忆. 肠道微生物组通过抑制PI3K/Akt信号传输来调解这种损伤,从而导致海马体受损.
科学领域:
- 神经科学是一个神经科学.
- 环境健康 环境健康
- 微生物学 微生物学
背景情况:
- 在中枢神经系统中积累了N-(1,3-二甲基) -N'--p-phenylenediamine-quinone (6PPD-Q).
- 6PPD-Q在认知障碍中的确切作用及其机制尚未完全理解.
研究的目的:
- 研究6PPD-Q对认知功能的影响.
- 阐明潜在的机制,包括肠道微生物组和PI3K/AKT信号的作用.
主要方法:
- 莫里斯水迷宫测试用于认知功能评估.
- 海马体的组织病理学分析 (HE染色).
- 便微生物群移植 (FMT) 实验.
- 西部Blot用于信号通路分析.
- 16S rDNA测序用于肠道微生物组的分析.
主要成果:
- 6PPD-Q显著影响学习和记忆.
- 观察到海马 (DG和CA3区域) 的改变,包括稀疏细胞和核凝结.
- 暴露于 FMT 的小鼠诱导了接受者的认知缺陷和海马损伤.
- 6PPD-Q暴露和FMT抑制了PI3K/AKT信号传递.
- 在肠道细菌属中发现了显著的变化 (例如,Helicobacter的上调,Prevotellaceae_NK3B31_组的下调).
结论:
- 肠道微生物组调解了6PPD-Q诱导的认知障碍.
- 抑制PI3K/Akt信号传递是6PPD-Q神经毒性的关键机制.
- 这些发现为探索针对6PPD-Q神经毒性的微生物向干预提供了基础.
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