title: The effect of arsenite on spatial learning: Involvement of autophagy and apoptosis.
abstract: Spatial learning plays a major role in one's information recording. Arsenic is one of ubiquitous environmental toxins with known neurological effects. However, studies investigating the effects of arsenic on spatial learning and related mechanisms are limited. This study was planned toexaminethe effects of bilateral intra-hippocampal infusion of different concentrations of sodium arsenite (5, 10 and 100nM, 5µl/side) on spatial learning in Wistar rats. Moreover, we evaluated levels of LC3-II, Atg7 and Atg12 as reliable biomarkers of autophagy and caspase-3 and Bax/Bcl-2 ratio as indicators of apoptosis in the hippocampus. Interestingly, low concentrations of sodium arsenite (5 and 10nM) significantly increased spatial acquisition but pre-training administration of sodium arsenite100nM did not significantly alter spatial learning. LC3-II levels were significantly increased in groups treated with sodium arsenite 5 and 10nM and decreased in the group receiving arsenite 100nM compared to the control group. Atg7 and Atg12 levels were obviously higher in all groups treated with sodium arsenite compared to control. However, caspase-3 cleavage and Bax/Bcl-2 ratio were notably greater in 100nM, and lesser in 5nM arsenite group in comparison with control animals. The results of this study showed that the low concentrations of sodium arsenite could facilitate spatial learning. This facilitation could be attributed to neuronal autophagy induced by low concentrations of sodium arsenite. These findings may help to clarify the regulatory pathways for apoptosis and autophagy balance due to sodium arsenite.
authors.affiliation: Department of Pharmacology and Toxicology, Faculty of Pharmacy, Toxicology and poisoning Research Centre, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Behnoosh
authors.initials: B
authors.lastname: BonakdarYazdi
authors.affiliation: Neuroscience Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
authors.forename: Fariba
authors.initials: F
authors.lastname: Khodagholi
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, Azad University, Qom, Iran.
authors.forename: Azadeh
authors.initials: A
authors.lastname: Sharifzadeh
authors.affiliation: Department of Physiology, Azad University, Qom, Iran.
authors.forename: Ramesh
authors.initials: R
authors.lastname: Ahmadi
authors.affiliation: Department of Pharmacology and Toxicology, Faculty of Pharmacy, Toxicology and poisoning Research Centre, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Mehdi
authors.initials: M
authors.lastname: Sanati
authors.affiliation: Department of Pharmacology and Toxicology, Faculty of Pharmacy, Toxicology and poisoning Research Centre, Tehran University of Medical Sciences, Tehran, Iran; Department of Neuroscience, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Hajar
authors.initials: H
authors.lastname: Mehdizadeh
authors.affiliation: Department of Pharmacology and Toxicology, Faculty of Pharmacy, Toxicology and poisoning Research Centre, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Borna
authors.initials: B
authors.lastname: Payandehmehr
authors.affiliation: Department of Medical Laboratory Sciences, Faculty of Allied Health Sciences, Kuwait University, Sulaibekhat, Kuwait.
authors.forename: Leila
authors.initials: L
authors.lastname: Vali
authors.affiliation: Physiology Department, School of Medicine, Lorestan University of Medical Sciences, Khoramabad, Iran.
authors.forename: Mehrnoush Moghaddasi
authors.initials: MM
authors.lastname: Jahromi
authors.affiliation: Department of Pharmacology and Toxicology, Faculty of Pharmacy, Toxicology and poisoning Research Centre, Tehran University of Medical Sciences, Tehran, Iran; Department of Neuroscience, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran; Department of Occupational Therapy, Faculty of Rehabilitation Sciences, Iran University of Medical Sciences, Tehran, Iran.
authors.forename: Ghorban
authors.initials: G
authors.lastname: Taghizadeh
authors.affiliation: Department of Pharmacology and Toxicology, Faculty of Pharmacy, Toxicology and poisoning Research Centre, Tehran University of Medical Sciences, Tehran, Iran; Department of Neuroscience, School of Advanced Technologies in Medicine, 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: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D018053:Arsenites / Q000494:pharmacology*; D001343:Autophagy / Q000187:drug effects*; D015415:Biomarkers / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D008297:Male; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D051381:Rats; D017670:Sodium Compounds / Q000494:pharmacology*; D065853:Spatial Learning / Q000187:drug effects*; D051028:bcl-2-Associated X Protein / Q000378:metabolism
chemical_list: D018053:Arsenites; D015415:Biomarkers; D019253:Proto-Oncogene Proteins c-bcl-2; D017670:Sodium Compounds; D051028:bcl-2-Associated X Protein; C017947:sodium arsenite
keywords: Alzheimer disease; Apoptosis; Autophagy; Caspase-3; LC3; Sodium arsenite; Spatial learning