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Influence of Zinc on Calcium-Dependent Signal Transduction Pathways During Aluminium-Induced Neurodegeneration

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Abstract

Metals perform important functions in the normal physiological system, and alterations in their levels may lead to a number of diseases. Aluminium (Al) has been implicated as a major risk factor, which is linked to several neurodegenerative diseases including Alzheimer’s disease and Parkinson’s disease. On the other hand, zinc (Zn) is considered as a neuromodulator and an essential dietary element that regulates a number of biological activities in our body. The aim of the present study was to investigate the effects of Zn supplementation, if any, in ameliorating the changes induced by Al on calcium signalling pathway. Male Sprague Dawley rats weighing 140–160 g were divided into four different groups viz.: normal control, aluminium treated (100 mg/kg b.wt./day via oral gavage), zinc treated (227 mg/l in drinking water) and combined aluminium and zinc treated. All the treatments were carried out for a total duration of 8 weeks. Al treatment decreased the Ca2+ ATPase activity whereas increased the levels of 3′, 5′-cyclic adenosine monophosphate, intracellular calcium and total calcium content in both the cerebrum and cerebellum, which, however, were modulated upon Zn supplementation. Al treatment exhibited a significant elevation in the protein expressions of phospholipase C, inositol triphosphate and protein kinase A but decreased the expression of protein kinase C, which, however, was reversed upon Zn co-treatment. Al treatment also revealed alterations in neurohistoarchitecture in the form of calcium deposits, which were improved upon zinc co-administration. The present study, therefore, suggests that zinc regulates the intracellular calcium signalling pathway during aluminium-induced neurodegeneration.

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Abbreviations

Al:

Aluminium

Zn:

Zinc

Ca:

Calcium

PLC:

Phospholipase C

IP3:

Inositol triphosphate

PKA:

Protein kinase A

PKC:

Protein kinase C

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Acknowledgments

Authors are thankful to Department of Biophysics, Panjab University, Chandigarh, India for providing various facilities during this study. Authors are also grateful to Mr. Damodar Dass, Senior Technician in Department of Biophysics, Panjab University, for providing valuable suggestions during staining procedures. We are grateful to University Grants Commission (UGC), New Delhi, India and Department of Science and Technology (DST-INSPIRE), New Delhi, India for financial support.

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The authors declare that there are no conflicts of interest.

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  1. Neha Singla

    Present address: Department of Biophysics, Postgraduate Institute of Medical Education and Research, Chandigarh, 160012, India

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

    Neha Singla & D. K. Dhawan

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Singla, N., Dhawan, D.K. Influence of Zinc on Calcium-Dependent Signal Transduction Pathways During Aluminium-Induced Neurodegeneration. Mol Neurobiol 50, 613–625 (2014). https://doi.org/10.1007/s12035-014-8643-7

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