罗亚/ROCK2信号通路调节了Mn诱导的紧结蛋白质的改变,导致小鼠的认知功能障碍
Yan Ma1, Honggang Chen1, Yuxin Jiang1
1Department of Occupational & Environmental Health and the Ministry of Education Key Lab of Hazard Assessment and Control in Special Operational Environment, School of Public Health, Fourth Military Medical University, Chang Le Xi Road, Xi'an,Shaanxi 710032, China.
Current research in toxicology
|January 21, 2025
概括
(Mn) 暴露会通过减少紧结蛋白 (TJPs) 来破坏血脑屏障 (BBB). 加斯特罗丁 (GAS) 通过恢复TJPs和调节RhoA/ROCK2通路来保护Mn诱导的认知缺陷.
科学领域:
- 神经科学是一个神经科学.
- 毒理学 毒理学 毒理学
- 药理学 药理学是指药理学的学科.
背景情况:
- 较高的 (Mn) 暴露与神经系统疾病有关,包括认知缺陷.
- Mn诱导的神经毒性涉及血脑屏障 (BBB) 的破坏,但机制尚不清楚.
- 紧结蛋白 (TJPs) 对BBB完整性至关重要.
研究的目的:
- 阐明与TJPs相关的Mn诱导BBB干扰的机制.
- 为了研究胃素 (GAS) 作为一种神经保护策略,防止Mn诱导的认知障碍.
主要方法:
- 在小鼠和细胞培养中开发了Mn暴露模型.
- 评估了TJP的表达和BBB的完整性.
- 评估了胃素 (GAS) 管理的影响.
主要成果:
- 暴露显著降低了TJP表达,导致BBB中断,无论是在生物体内还是体外.
- 过度表达的奥克卢丁 (OCLN) 缓解了Mn诱导的BBB损伤.
- 气体管理减轻了BBB干扰,增强了TJP表达,并改善了认知功能,可能通过RhoA/ROCK2通路.
结论:
- 暴露会通过降低TJPs的调节来破坏BBB,从而导致认知缺陷.
- 通过维护BBB的完整性,Gastrodin (GAS) 证明了对Mn毒性的神经保护作用.
- 调节RhoA/ROCK2通路是GAS治疗作用的一个潜在机制.
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