title: How sodium arsenite improve amyloid β-induced memory deficit?
abstract: Evidence has shown that arsenic exposure, besides its toxic effects results in impairment of learning and memory, but its molecular mechanisms are not fully understood. In the present study, we examined sodium arsenite (1, 5, 10, 100nM) effects on contextual and tone memory of male rats in Pavlovian fear conditioning paradigm alone and in co-administration with β-amyloid. We detected changes in the level of caspase-3, nuclear factor kappa-B (NF-κB), cAMP response element-binding (CREB), heme oxygenase-1 and NF-E2-related factor-2 (Nrf2) by Western blot. Sodium arsenite in high doses induced significant memory impairment 9 and 16days after infusion. By contrast, low doses of sodium arsenite attenuate memory deficit in Aβ injected rats after 16days. Our data revealed that treatment with high concentration of sodium arsenite increased caspase-3 cleavage and NF-κB level, 9days after injection. Whereas, low doses of sodium arsenite cause Nrf2 and HO-1 activation and increased CREB phosphorylation in the hippocampus. These findings suggest the concentration dependent effects of sodium arsenite on contextual and tone memory. Moreover, it seems that the neuroprotective effects of ultra-low concentrations of sodium arsenite on Aβ-induced memory impairment is mediated via an increase Nrf2, HO-1 and CREB phosphorylation levels and decrease caspase-3 and NF-κB amount.
authors.affiliation: Department of Pharmacology and Toxicology, Pharmaceutical Sciences Research Center, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Ehsan
authors.initials: E
authors.lastname: Nassireslami
authors.affiliation: Department of Pharmacology and Toxicology, Pharmaceutical Sciences Research Center, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Parmida
authors.initials: P
authors.lastname: Nikbin
authors.affiliation: Department of Pharmacology and Toxicology, Pharmaceutical Sciences Research Center, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Elham
authors.initials: E
authors.lastname: Amini
authors.affiliation: Department of Pharmacology and Toxicology, Pharmaceutical Sciences Research Center, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Borna
authors.initials: B
authors.lastname: Payandemehr
authors.affiliation: Department of Physiology, Faculty of Medicine, Hormozgan University of Medical Sciences, Bandar Abbas, Iran.
authors.forename: Fatemeh
authors.initials: F
authors.lastname: Shaerzadeh
authors.affiliation: Department of Physiology, Faculty of Medicine, Hormozgan University of Medical Sciences, Bandar Abbas, Iran; Neuroscience Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
authors.forename: Fariba
authors.initials: F
authors.lastname: Khodagholi
authors.affiliation: Department of Pharmacology and Toxicology, Pharmaceutical Sciences Research Center, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Behnoosh Bonakdar
authors.initials: BB
authors.lastname: Yazdi
authors.affiliation: Department of Pharmacology and Toxicology, Pharmaceutical Sciences Research Center, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Abbas
authors.initials: A
authors.lastname: Kebriaeezadeh
authors.affiliation: Department of Neuroscience, Faculty of Advanced Science and Technology in Medicine, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Ghorban
authors.initials: G
authors.lastname: Taghizadeh
authors.affiliation: Department of Pharmacology and Toxicology, Pharmaceutical Sciences Research Center, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran. Electronic address: msharifzadeh@sina.tums.ac.ir.
authors.forename: Mohammad
authors.initials: M
authors.lastname: Sharifzadeh
mesh_terms: D016229:Amyloid beta-Peptides / Q000009:adverse effects*; D000818:Animals; D018053:Arsenites / Q000494:pharmacology / Q000627:therapeutic use*; D050882:CREB-Binding Protein / Q000378:metabolism; D053148:Caspase 3 / Q000378:metabolism; D003214:Conditioning, Classical / Q000187:drug effects; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D005239:Fear / Q000187:drug effects; D046352:Freezing Reaction, Cataleptic / Q000187:drug effects; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008569:Memory Disorders / Q000139:chemically induced* / Q000188:drug therapy*; D009043:Motor Activity / Q000187:drug effects; D010446:Peptide Fragments / Q000009:adverse effects*; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction / Q000187:drug effects; D017670:Sodium Compounds / Q000494:pharmacology / Q000627:therapeutic use*; D013997:Time Factors
chemical_list: D016229:Amyloid beta-Peptides; D018053:Arsenites; D004791:Enzyme Inhibitors; D010446:Peptide Fragments; D017670:Sodium Compounds; C075222:amyloid beta-protein (1-42); C017947:sodium arsenite; D050882:CREB-Binding Protein; D053148:Caspase 3
keywords: Alzheimer's disease; Amyloid β; CREB; Nrf2; Oxidative stress; Sodium arsenite