The effect of arsenite on spatial learning: Involvement of autophagy and apoptosis

Mehrnoush Moghaddasi Jahromi, Lorestan University of Medical Sciences and Behnoosh BonakdarYazdi, Tehran University of Medical Sciences and Fariba Khodagholi, Shahid Beheshti University of Medical Sciences and Fatemeh Shaerzadeh, Hormozgan University of Medical Sciences and Azadeh Sharifzadeh, Azad University, Qom, Iran and Mehdi Sanati, Tehran University of Medical Scienc and Hajar Mehdizadeh, Tehran University of Medical Scienc and Borna Payandehmehra, Tehran University of Medical Scienc and Leila Vali, Faculty of Allied Health Sciences, Kuwait University and Ghorban Taghizadeh, Tehran University of Medical Sciences and Mohammad Sharifzadeh, Tehran University of Medical Sciences (2016) The effect of arsenite on spatial learning: Involvement of autophagy and apoptosis. European Journal of Pharmacology, 796 (2017). pp. 54-61. ISSN 0014-2999

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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 100 nM, 5 μl/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 10 nM) significantly increased spatial acquisition but pre-training administration of sodium arsenite100 nM did not significantly alter spatial learning. LC3-II levels were significantly increased in groups treated with sodium arsenite 5 and 10 nM and decreased in the group receiving arsenite 100 nM 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 100 nM, and lesser in 5 nM 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. Keywords: Sodium arsenite Autophagy Apoptosis Alzheimer disease Spatial learning Caspase-3 LC3

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