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基础科学和病原发生学

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长期暴露于 (Cd) 和 (Pb) 会恶化认知衰退和阿尔茨海默氏症.

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科学领域:

  • 神经科学是一个神经科学.
  • 毒理学 毒理学 毒理学
  • 细胞生物学 细胞生物学

背景情况:

  • 流行病学研究将 (Cd) 和 (Pb) 等重金属暴露与阿尔茨海默病 (AD) 风险增加联系起来.
  • 通过Cd和Pb影响AD病变的精确细胞和分子机制在很大程度上是未知的.
  • 本研究调查了Cd和Pb暴露对5xFAD小鼠模型认知功能和AD进展的影响.

研究的目的:

  • 确定慢性暴露于 (Cd) 和 (Pb) 如何影响5xFAD老鼠阿尔茨海默病 (AD) 模型中的认知功能.
  • 为了阐明由Cd和Pb暴露导致AD病变的恶化背后的细胞和分子机制.

主要方法:

  • 5xFAD小鼠在饮用水中暴露于 (Pb) 或 (Cd) 6周.
  • 用Y迷宫和开放场迷宫测试来评估认知功能.
  • 衰老标志物,衰老相关分泌表型 (SASP) 细胞因子和神经炎症标志物使用RT-PCR,免疫光和共聚焦显微镜进行了分析.

主要成果:

  • 暴露于Cd和Pb都加速了5xFAD小鼠的粉样β (Aβ) 斑块形成和认知衰退.
  • 即使在较低剂量中,Cd暴露在加剧Aβ沉积和认知缺陷方面也比Pb更强大.
  • 暴露于Cd增加了p16Ink4a衰老标志物和IL-6表达,特别是在海马体,并在微质细胞中诱导过早衰老.

结论:

  • 在5xFAD小鼠中,长期暴露于Cd或Pb会加剧认知缺陷和阿尔茨海默病 (AD) 的进展.
  • 通过增加海马体中衰老细胞负担和神经炎症,CD暴露加速了AD的进展.
  • 由Cd诱导的衰老微质细胞通过IL-6释放促进神经炎症.