Expression of DnMTs and MBDs in AlCl 3 -Induced Neurotoxicity Mouse Model
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Expression of DnMTs and MBDs in AlCl3-Induced Neurotoxicity Mouse Model Muhammad Faisal Ikram 1,2 & Syeda Mehpara Farhat 3,4 & Aamra Mahboob 3 & Saeeda Baig 5 & Ahmed Yaqinuddin 1 & Touqeer Ahmed 3 Received: 6 August 2020 / Accepted: 3 November 2020 # Springer Science+Business Media, LLC, part of Springer Nature 2020
Abstract 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. Keywords Epigenetic alterations . Environmental toxins . DNA methylation . Aluminum . Animal model . Alzheimer’s disease
Introduction Aluminum is the third most abundant element in the earth’s crust with no known biological functions [1], and therefore, it has been considered safe for human health. This concept has consequently
* Touqeer Ahmed [email protected]; [email protected] 1
Department of Anatomy, College of Medicine, Alfaisal University, Riyadh, Kingdom of Saudi Arabia
2
Medical College, Ziauddin University, Karachi, Pakistan
3
Neurobiology Laboratory, Department of Healthcare Biotechnology, Atta-ur-Rahman School of Applied Biosciences, National University of Sciences and Technology (NUST), Sector H-12, Islamabad 44000, Pakistan
4
Department of Biological Sciences, National University of Medical Sciences, Rawalpindi 46000, Pakistan
5
Department of Biochemistry, Ziauddin University, Karachi, Pakistan
resulted in wide use of Al in processing, packing, and storing food [2]. High Al transportation from rocks to drinking water, due to acid rain, and w
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