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Selective Inducible Nitric Oxide Synthase Inhibitor Reversed Zinc Chloride-Induced Spatial Memory Impairment via Increasing Cholinergic Marker Expression

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Abstract

Zinc, an essential micronutrient and biochemical element of the human body, plays structural, catalytic, and regulatory roles in numerous physiological functions. In the current study, the effects of a pretraining oral administration of zinc chloride (10, 25, and 50 mg/kg) for 14 consecutive days and post-training bilateral intra-hippocampal infusion of 1400W as a selective inducible nitric oxide synthase (iNOS) inhibitor (10, 50, and 100 μM/side), alone and in combination, on the spatial memory retention in Morris water maze (MWM) were investigated. Animals were trained for 4 days and tested 48 h after completion of training. Also, the molecular effects of these compounds on the expression of choline acetyltransferase (ChAT), as a cholinergic marker in the CA1 region of the hippocampus and medial septal area (MSA), were evaluated. Behavioral and molecular findings of this study showed that a 2-week oral administration of zinc chloride (50 mg/kg) impaired spatial memory retention in MWM and decreased ChAT expression. Immunohistochemical analysis of post-training bilateral intra-hippocampal infusion of 1400W revealed a significant increase in ChAT immunoreactivity. Furthermore, post-training bilateral intra-hippocampal infusion of 1400W into the CA1 region of the hippocampus reversed zinc chloride-induced spatial memory impairment in MWM and significantly increased ChAT expression in comparison with zinc chloride-treated animals. Taken together, these results emphasize the role of selective iNOS inhibitors in reversing zinc chloride-induced spatial memory deficits via modulation of cholinergic marker expression.

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Acknowledgments

This work was supported by Tehran University of Medical Sciences (grant number 6093).

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Authors and Affiliations

  1. Department of Pharmacology and Toxicology, Faculty of Pharmacy, Zabol University of Medical Sciences, Zabol, Iran

    Kaveh Tabrizian

  2. Family Health Research Center, Iranian Petroleum Industry Health Research Institute, Tehran, Iran

    Kian Azami

  3. Department of Physiology, Faculty of Medicine, Tehran University of Medical Sciences, Tehran, Iran

    Maryam Belaran

  4. Department of Toxicology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran

    Maliheh Soodi

  5. Department of Medicinal Chemistry, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran

    Khosrou Abdi

  6. Department of Pharmacology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran

    Sahar Fanoudi

  7. Department of Pharmacology and Toxicology, Faculty of Pharmacy, Tehran University of Medical Sciences, P.O. Box 14155-6451, Tehran, Iran

    Mehdi Sanati, Negar Mottaghi Dastjerdi, Mohammad Soltany rezaee-Rad & Mohammad Sharifzadeh

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  1. Kaveh Tabrizian
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Tabrizian, K., Azami, K., Belaran, M. et al. Selective Inducible Nitric Oxide Synthase Inhibitor Reversed Zinc Chloride-Induced Spatial Memory Impairment via Increasing Cholinergic Marker Expression. Biol Trace Elem Res 173, 443–451 (2016). https://doi.org/10.1007/s12011-016-0679-2

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