Expression of DnMTs and MBDs in AlCl₃-Induced Neurotoxicity Mouse Model

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 AlCl₃ 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 AlCl₃ showed significant cognitive deficit with impaired short-term memory, elevated anxiety, and deterioration in spatial and reference memory. The AlCl₃ treatment showed significant reduction in the expression of MBDs in the whole cortex at 60 days of treatment as compared to control. AlCl₃-treated animals showed decreased expression of MBDs and DnMT3a in the hippocampus for longer treated animals but strikingly, MBD2 showed significantly increased expression in AlCl₃-treated animals at 60 days p ≤ 0.001. In conclusion, this study showed that AlCl₃-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.