阿托瓦斯塔丁可以挽救因高血糖蛋白质血症引起的认知缺陷和神经炎症基因变化
Erica M Weekman1,2, Sherika N Johnson3,4, Colin B Rogers3
1Sanders-Brown Center on Aging, University of Kentucky, Lexington, KY, 40536, USA. eweekman@iu.edu.
Journal of neuroinflammation
|September 1, 2023
概括
阿托瓦斯塔丁通过降低同类氨酸和恢复基因表达,而不是通过影响血管完整性,改善了患有高同类氨酸血症的小鼠的认知能力. 这表明了血管对认知障碍和痴呆的贡献的潜在治疗策略.
科学领域:
- 神经科学是一个神经科学.
- 药理学 药理学是指药理学的学科.
背景情况:
- 流行病学研究表明,他类药物可能会降低痴呆风险,特别是阿尔茨海默病 (AD).
- 临床前的证据表明,他类药物不仅仅是降低胆固醇,而且还能预防痴呆症.
- 血管对认知障碍和痴呆症 (VCID) 的贡献,通常与AD并发,是认知衰退的重要原因.
研究的目的:
- 在小鼠模型中,研究阿托瓦斯塔丁是否能改善高同位素血症 (HHcy) 引起的VCID.
- 确定阿托瓦斯塔丁潜在神经保护作用背后的机制.
主要方法:
- 给小鼠诱导HHcy或控制饮食,有或没有阿托瓦斯塔丁,持续14周.
- 用新的对象识别测试来评估认知功能.
- 分析了等离子体生物标志物,质基因表达 (qPCR,NanoString),微质形态,星球细胞末端脚和微出血.
主要成果:
- 在HHcy小鼠中,阿托瓦斯塔丁降低了血总同型半氨酸,但没有改变胆固醇水平.
- 由HHcy诱导的质基因表达变化被阿托瓦斯塔丁挽救,特别是在寡细胞和微细胞中.
- 阿托瓦斯塔丁治疗改善了新型物体识别任务中的认知表现.
- 虽然观察到趋势,但阿托瓦斯塔丁并没有显著影响微型出血或天体细胞末端.
结论:
- 阿托尔瓦斯塔丁可以挽救HHcy诱导的认知缺陷,很可能是通过降低血类固醇蛋白和恢复质基因表达.
- 这些发现表明,阿托瓦斯塔丁的益处独立于直接改善血管完整性或显著的微质形态变化.
- 阿托瓦斯塔丁在缓解VCID方面表现有前途,可能通过除降低胆固醇之外的机制.
关键词:
星球细胞末端的脚一个阿托尔瓦斯塔丁.胆固醇 胆固醇 胆固醇过高homocysteinemia 过高homocysteinemia 过高homocysteinemia 过高homocysteinemia 过高homocysteinemia 过高homocysteinemia 过高homocysteinemia 过高homocysteinemia 过高homocysteinemia 过高homocysteinemia 过高homocysteinemia微质细胞中的微质细胞微出血是一种微出血.神经炎症是一种神经炎症.血管对认知障碍和痴呆症的贡献更多相关视频
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