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Cortex- and Amygdala-Dependent Learning and Nicotinic Acetylcholine Receptor Gene Expression is Severely Impaired in Mice Orally Treated with AlCl3

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Abstract

Recent industrialization has increased human exposure to bio-available aluminum (Al). If more Al enters the brain than leaves, Al concentration will rise in the brain leading to neurodegenerative disorders. The aim of the present study was to determine Al concentration, neurodegeneration, and nicotinic acetylcholine receptor (nAChR) gene expression in the cortex and amygdala after oral ingestion of Al salt. The effect of Al on cortex- and amygdala-dependent learning and memory functions was also assessed. Mice were given AlCl3 (250 mg/kg) in drinking water for 42 days. nAChR gene expression was determined in the cortex and amygdala. The mice were subjected to behavior tests (fear conditioning, fear extinction, and open field), to assess memory deficits. The acquisition of fear memory in the fear conditioning test remained unaffected due to the Al administration. However, fear extinction (which is a new learning) was severely impaired. The behavioral analysis in the open field test showed greater anxiety and less adaptability to the new environment in Al-treated animals. High Al concentration and severe neurodegeneration in the cortex were observed following Al treatment while a slight, non-significant elevation in Al concentration was observed in the amygdala of Al-treated animals. The analysis of nAChR gene expression via RT-PCR showed a significant reduction in expression of α7, α4, and β2 nAChR genes in the cortex of Al-treated animals, while in the amygdala, the level of the α4 nAChR gene remained unaltered. Oral Al ingestion causes neuropathological changes and suppresses expression of nAChR genes that lead to deficits in learning and higher anxiety in Al-treated animals.

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Acknowledgements

We are thankful to the Atta-ur-Rahman School of Applied Biosciences, National University of Sciences and Technology, Islamabad, Pakistan, for providing funding, support, and research facilities to carry out this research project.

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  1. Neurobiology Laboratory, Department of Healthcare Biotechnology, Atta-ur-Rahman School of Applied Biosciences, National University of Sciences and Technology, Sector H-12, Islamabad, 44000, Pakistan

    Syeda Mehpara Farhat, Aamra Mahboob & Touqeer Ahmed

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  1. Syeda Mehpara Farhat
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Correspondence to Touqeer Ahmed.

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All applicable international, national, and institutional guidelines for the care and use of animals were followed. This article does not contain any studies with human participants performed by any of the authors.

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Farhat, S.M., Mahboob, A. & Ahmed, T. Cortex- and Amygdala-Dependent Learning and Nicotinic Acetylcholine Receptor Gene Expression is Severely Impaired in Mice Orally Treated with AlCl3 . Biol Trace Elem Res 179, 91–101 (2017). https://doi.org/10.1007/s12011-017-0942-1

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