母亲双A暴露诱导海马体依赖的学习和记忆缺陷通过PI3K/Akt/mTOR途径在雄性后代大鼠
Jiajia Ren1, Wenjie Bai1,2, Yi Guo1
1College of Health Public, Shaanxi University of Chinese Medicine, Xianyang, China.
Journal of biochemical and molecular toxicology
|January 12, 2025
概括
母亲接触到双A (BPA) 会损害后代的学习和记忆. 这种神经认知衰退与PI3K/Akt/mTOR通路的破坏和海马体中氧化应激增加有关.
科学领域:
- 环境毒理学环境毒理学
- 神经科学是一个神经科学.
- 内分泌学 在内分泌学.
背景情况:
- 双A (BPA) 是一种广泛存在的内分泌干扰化学物质,已知与异常认知行为有关.
- 在BPA的神经认知作用的基础上,尤其是发育过程中的精确机制,仍然不完全理解.
- 鉴于BPA在食品,水和环境中无处不在,了解这些机制至关重要.
研究的目的:
- 调查母亲对双A (BPA) 暴露对男性后代空间学习和记忆的影响.
- 阐明潜在的神经生物学机制,重点关注PI3K/Akt/mTOR信号通路和氧化应激和神经元损伤的标志物.
主要方法:
- 怀孕的Sprague Dawley大鼠从胚胎的第0天到产后的第21天暴露于不同剂量的BPA (0,0.04,0.4,4毫克/公斤/天)
- 在男性后代中使用莫里斯水迷宫测试来评估空间学习和记忆.
- 河马蛋白质表达 (PI3K/Akt/mTOR通路,GSK3β,p-tau),马隆迪阿尔代海德 (MDA) 和卡斯帕斯-3活性通过西布洛特和生物化学测试进行了分析.
主要成果:
- 暴露于BPA显著损害了男性后代的空间学习和记忆,通过增加逃跑延迟和减少平台穿越时间来证明这一点.
- 母亲BPA暴露降低了海马中的PI3K/Akt/mTOR/p70S6K通路的调节.
- BPA增加了GSK3β和化陶水平,增加了MDA,并激活了caspase-3,表明氧化应激和神经元损伤.
结论:
- 母亲接触到双A会诱导男性后代显著的学习和记忆缺陷.
- PI3K/Akt/mTOR信号通路在BPA引起的神经认知障碍中发挥着关键作用.
- 这些发现强调BPA是一种神经发育毒素,对认知功能有长期影响.
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