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Mol Neurobiol. 2017 Jan;54(1):406-422. doi: 10.1007/s12035-015-9653-9. Epub 2016 Jan 7.

Zinc Improves Cognitive and Neuronal Dysfunction During Aluminium-Induced Neurodegeneration.

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Department of Biophysics, Sector-14, Panjab University, Chandigarh, 160014, India.
Department of Biophysics, Sector-14, Panjab University, Chandigarh, 160014, India.


Metals are considered as important components of a physiologically active cell, and imbalance in their levels can lead to various diseased conditions. Aluminium (Al) is an environmental neurotoxicant, which is etiologically related to several neurodegenerative disorders like Alzheimer's, whereas zinc (Zn) is an essential trace element that regulates a large number of metabolic processes in the brain. The objective of the present study was to understand whether Zn provides any physiological protection during Al-induced neurodegeneration. Male Sprague Dawley rats weighing 140-160 g received either aluminium chloride (AlCl3) orally (100 mg/kg b.wt./day), zinc sulphate (ZnSO4) in drinking water (227 mg/L) or combined treatment of aluminium and zinc for 8 weeks. Al treatment resulted in a significant decline in the cognitive behaviour of rats, whereas zinc supplementation caused an improvement in various neurobehavior parameters. Further, Al exposure decreased (p ≤ 0.001) the levels of neurotransmitters, acetylcholinesterase activity, but increased (p ≤ 0.001) the levels of L-citrulline as well as activities of nitric oxide and monoamine oxidase in the brain. However, zinc administration to Al-treated animals increased the levels of neurotransmitters and regulated the altered activities of brain markers. Western blot of tau, amyloid precursor protein (APP), glial fibrillary acidic protein (GFAP), ubiquitin, α-synuclein and Hsp 70 were also found to be elevated after Al exposure, which however were reversed following Zn treatment. Al treatment also revealed alterations in neurohistoarchitecture in the form of loss of pyramidal and Purkinje cells, which were improved upon zinc co-administration. Therefore, the present study demonstrates that zinc improves cognitive functions by regulating α-synuclein and APP-mediated molecular pathways during aluminium-induced neurodegeneration.


Aluminium; Behaviour; Brain markers; Neurodegeneration; Neurotransmitters; Zinc

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