Effects of inorganic arsenic exposure on glucose transporters and insulin receptor in the hippocampus of C57BL/6 male mice

• Published in: Neurotoxicology and teratology 2016-03, Vol.54, p.68-77
• Main Authors: Rodríguez, V.M, Limón-Pacheco, J.H, Del Razo, L.M, Giordano, M
• Format: Article
• Language: English
• Subjects: Animals; Arsenic; Arsenic Poisoning - pathology; Arsenicals - pharmacology; Blood Glucose - drug effects; Dose-Response Relationship, Drug; Drinking water; Emergency; Gene Expression Regulation - drug effects; Glucose; Glucose Tolerance Test; Glucose Transport Proteins, Facilitative - genetics; Glucose Transport Proteins, Facilitative - metabolism; Hippocampus; Hippocampus - drug effects; Hippocampus - metabolism; Locomotion - drug effects; Male; Maze Learning - drug effects; Medical Education; Mice; Mice, Inbred C57BL; Receptor, Insulin - genetics; Receptor, Insulin - metabolism; RNA, Messenger - metabolism; Statistics, Nonparametric
• ISSN: 0892-0362; 1872-9738
• DOI: 10.1016/j.ntt.2016.02.001

Abstract Children and adolescent populations chronically exposed to high doses of inorganic arsenic (i As) in drinking water in some regions around the world have shown behavioral and memory deficits. Recent studies have also associatedi As exposure with dysregulation of glucose metabolism. The hippocampus is a cerebral region well known for its role in learning and memory. Studies in vitro and in vivo have shown that the hippocampus is vulnerable toi As exposure, and to changes in glucose metabolism. The glucose transporters (GLUTs) and insulin receptor (IR) regulate glucose metabolism in brain; they are expressed by hippocampal cells, and alterations in these proteins have been associated with memory deficits. The aims of this study were to evaluate the effects ofi As exposure via drinking water (DW) on GLUT1 , GLUT3 and insulin receptor ( INSR ) mRNA expression in the hippocampus, on performance in a spatial memory task, and on peripheral glucose regulation. C57Bl/6 male mice were exposed to 50 mgi As/L via DW for one, two, or three months. The qRT-PCR analyses indicated that, compared to a control group, GLUT1 and GLUT3 mRNA levels were decreased, while INSR mRNA levels were increased in the hippocampus ofi As exposed animals. The levels ofi As and its methylated species in the hippocampus of thei As-exposed group were significantly higher than in controls. Mice exposed toi As learned the spatial task but showed increased latency to find the submerged platform 48 h after the last training session; these animals also showed dysregulation of peripheral glucose. These results suggest that the effects ofi As exposure on a spatial memory task performance could be mediated by disruptions of glucose regulation in the CNS.