Department of Anatomy, College of Medicine, Alfaisal University, Riyadh, Kingdom of Saudi Arabia.
Medical College, Ziauddin University, Karachi, Pakistan.
Biol Trace Elem Res. 2021 Sep;199(9):3433-3444. doi: 10.1007/s12011-020-02474-4. Epub 2020 Nov 11.
Alteration in DNA methylation after aluminum exposure has been shown to contribute in pathogenesis of Alzheimer's disease (AD). This study is aimed to determine the effect of Al exposure (42 and 60 days) on learning and memory and the expression of proteins involved in DNA methylation (MBD1, MBD2, MBD3, MeCP2 (methyl CpG binding protein 2), DnMT1 and DnMT3a). Male BALB/c mice were treated with AlCl for either 42 days or 60 days. After treatment completion, learning and memory were compared to the control group using novel object recognition test, elevated plus maze test, open field test, and Morris water maze test. The treated animals and their respective controls were sacrificed after cognitive testing and samples from their whole cortex and hippocampus were harvested for gene expression analysis. Mice treated with AlCl showed significant cognitive deficit with impaired short-term memory, elevated anxiety, and deterioration in spatial and reference memory. The AlCl treatment showed significant reduction in the expression of MBDs in the whole cortex at 60 days of treatment as compared to control. AlCl-treated animals showed decreased expression of MBDs and DnMT3a in the hippocampus for longer treated animals but strikingly, MBD2 showed significantly increased expression in AlCl-treated animals at 60 days p ≤ 0.001. In conclusion, this study showed that AlCl-treated animals showed significant memory and cognitive deficits and it is associated with significant changes in the expression of proteins involved in DNA methylation mechanism. Moreover, different Al exposure duration had slightly different effects.
铝暴露后 DNA 甲基化的改变被认为有助于阿尔茨海默病 (AD) 的发病机制。本研究旨在确定铝暴露 (42 和 60 天) 对学习和记忆以及参与 DNA 甲基化的蛋白质表达的影响 (MBD1、MBD2、MBD3、MeCP2(甲基 CpG 结合蛋白 2)、DnMT1 和 DnMT3a)。雄性 BALB/c 小鼠用 AlCl 处理 42 天或 60 天。治疗完成后，通过新物体识别测试、高架十字迷宫测试、旷场测试和 Morris 水迷宫测试将学习和记忆与对照组进行比较。在认知测试后，处死接受治疗的动物及其各自的对照动物，并从其整个皮质和海马体采集样本进行基因表达分析。用 AlCl 处理的小鼠表现出明显的认知缺陷，伴有短期记忆受损、焦虑增加以及空间和参考记忆恶化。与对照组相比，60 天治疗时，AlCl 处理在整个皮质中显著降低了 MBDs 的表达。与对照组相比，AlCl 处理的动物在海马体中表现出 MBDs 和 DnMT3a 的表达减少，但令人惊讶的是，MBD2 在 60 天时在 AlCl 处理的动物中表达显著增加，p≤0.001。总之，本研究表明，AlCl 处理的动物表现出明显的记忆和认知缺陷，这与参与 DNA 甲基化机制的蛋白质表达的显著变化有关。此外，不同的铝暴露持续时间有略微不同的影响。
