title: Selective Inducible Nitric Oxide Synthase Inhibitor Reversed Zinc Chloride-Induced Spatial Memory Impairment via Increasing Cholinergic Marker Expression.
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.
authors.affiliation: Department of Pharmacology and Toxicology, Faculty of Pharmacy, Zabol University of Medical Sciences, Zabol, Iran.
authors.forename: Kaveh
authors.initials: K
authors.lastname: Tabrizian
authors.affiliation: Family Health Research Center, Iranian Petroleum Industry Health Research Institute, Tehran, Iran.
authors.forename: Kian
authors.initials: K
authors.lastname: Azami
authors.affiliation: Department of Physiology, Faculty of Medicine, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Maryam
authors.initials: M
authors.lastname: Belaran
authors.affiliation: Department of Toxicology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran.
authors.forename: Maliheh
authors.initials: M
authors.lastname: Soodi
authors.affiliation: Department of Medicinal Chemistry, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Khosrou
authors.initials: K
authors.lastname: Abdi
authors.affiliation: Department of Pharmacology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.
authors.forename: Sahar
authors.initials: S
authors.lastname: Fanoudi
authors.affiliation: Department of Pharmacology and Toxicology, Faculty of Pharmacy, Tehran University of Medical Sciences, P.O. Box 14155-6451, Tehran, Iran.
authors.forename: Mehdi
authors.initials: M
authors.lastname: Sanati
authors.affiliation: Department of Pharmacology and Toxicology, Faculty of Pharmacy, Tehran University of Medical Sciences, P.O. Box 14155-6451, Tehran, Iran.
authors.forename: Negar
authors.initials: N
authors.lastname: Mottaghi Dastjerdi
authors.affiliation: Department of Pharmacology and Toxicology, Faculty of Pharmacy, Tehran University of Medical Sciences, P.O. Box 14155-6451, Tehran, Iran.
authors.forename: Mohammad
authors.initials: M
authors.lastname: Soltany Rezaee-Rad
authors.affiliation: Department of Pharmacology and Toxicology, Faculty of Pharmacy, Tehran University of Medical Sciences, P.O. Box 14155-6451, Tehran, Iran. msharifzadeh@sina.tums.ac.ir.
authors.forename: Mohammad
authors.initials: M
authors.lastname: Sharifzadeh
mesh_terms: D000818:Animals; D056547:CA1 Region, Hippocampal / Q000201:enzymology* / Q000473:pathology / Q000503:physiopathology; D002712:Chlorides / Q000633:toxicity*; D002795:Choline O-Acetyltransferase / Q000096:biosynthesis*; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D006801:Humans; D007097:Imines / Q000494:pharmacology*; D008297:Male; D052247:Nitric Oxide Synthase Type II / Q000037:antagonists & inhibitors*; D051381:Rats; D017208:Rats, Wistar; D065852:Spatial Memory / Q000187:drug effects*; D017967:Zinc Compounds / Q000633:toxicity*
chemical_list: D002712:Chlorides; D004791:Enzyme Inhibitors; D007097:Imines; C496401:N-((3-(aminomethyl)phenyl)methyl)ethanimidamide; D017967:Zinc Compounds; C016837:zinc chloride; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat; D002795:Choline O-Acetyltransferase
keywords: CA1 region; Choline acetyltransferase; Inducible nitric oxide synthase inhibitor; Learning and memory; Medial septal area; Zinc chloride