通过调节PKA/CREB/Sirt1/eIF2α信号通路来改善缺血性中风后的认知功能
Ze-Jun Guo1, Lei Zhang2, Ling-Feng Wang3
1School of Pharmaceutical Sciences, ZheJiang Chinese Medical University, Hangzhou, 310053, China.
通过PKA/ CREB/ Sirt1/ eIF2α通路增强突触可塑性,改善了缺血性中风后的认知功能. 这种传统药物显示出治疗中风引起的认知障碍的潜力.
科学领域:
- 神经科学
- 药理学
- 传统中国医学
背景情况:
- 这是一种具有清除热量和增强认知功能的传统药物.
- 它用于认知障碍的缺血性中风,但机制需要阐明.
研究的目的:
- 研究BCS治疗缺血性中风引起的认知障碍的潜力.
- 探索其涉及突触可塑性和PKA/CREB/Sirt1/eIF2α通路的机制.
主要方法:
- 在ICR小鼠中建立了全球脑缺血/再输血 (GCI/ R) 模型.
- 使用行为测试评估认知功能和分析海马CA1区域组织学.
- 量化关键蛋白质表达与突触可塑性和信号通路通过西部斑块.
主要成果:
- BCS (10和15毫克/公斤) 显著改善了认知能力,并保持了神经元完整性.
- 在抑制PERK/eIF2α通路的同时,BCS上调了p-PKA,CREB和Sirt1.
- 这促进了突触重塑,由增加的PSD95和SYN1表达体现.
结论:
- 通过PKA/CREB/Sirt1/eIF2α途径增强海马突触可塑性.
- 这种机制促进神经元的存活,并改善缺血性中风模型中的认知功能.
- 在中风引起的认知障碍中, BCS 具有潜在的治疗作用.
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