Oral exposure to aluminum leads to reduced nicotinic acetylcholine receptor gene expression, severe neurodegeneration and impaired hippocampus dependent learning in mice

Drug Chem Toxicol. 2021 May;44(3):310-318. doi: 10.1080/01480545.2019.1587452. Epub 2019 Mar 20.


Aluminum (Al) is known for its neurotoxicity for over a century and is reported to have specifically high toxicity for cholinergic system. The effect of Al on muscarinic acetylcholine receptors is widely reported, but its effect on nicotinic acetylcholine receptors (nAChRs) is less well known. The aim of this study was to determine the effects of Al on hippocampus dependent learning and memory, function and expression of nAChRs in the hippocampus. Al concentration and neurodegeneration were also measured in the hippocampus following Al treatment. The mice were treated with 250 mg/kg AlCl3.6H2O in drinking water for a period of 42 days. Results show that Al treated animals have significantly reduced spatial reference memory as compared to control animals in Morris water maze test. Similarly, Al treated animals showed reduced contextual memory for Pavlovian fear compared to control animals. Al treated animals show higher anxiety in elevated plus maze as compared to control animals. The analysis of nAChR expression via RT-PCR showed reduced expression of α7, α4 and β2 nAChR gene expression in the hippocampus of Al treated animals. High Al accumulation was observed in Al-treated animals (688.14 ± 242.82 μg/g) compared to the control group (115.14 ± 18.18 μg/g) that resulted in severe neurodegeneration in the hippocampus. These results demonstrated that Al exposure caused neurotoxicity in mice hippocampus which is manifested by reduced memory and elevated anxiety. The results were further validated by high Al accumulation in the hippocampus, severe neurodegeneration and reduced expression of nAChRs.

Keywords: Morris water maze; Nicotinic acetylcholine receptors; contextual fear memory; elevated plus maze; histology; neurodegeneration.