1. Transcriptomic effects of depleted uranium on acetylcholine and cholesterol metabolisms in Alzheimer's disease model.
- Author
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Lestaevel P, Bensoussan H, Racine R, Airault F, Gourmelon P, and Souidi M
- Subjects
- Alzheimer Disease etiology, Alzheimer Disease genetics, Amyloid beta-Protein Precursor genetics, Animals, Carrier Proteins biosynthesis, Carrier Proteins genetics, Disease Models, Animal, Enzymes biosynthesis, Enzymes genetics, Frontal Lobe metabolism, Genetic Predisposition to Disease, Humans, Male, Mice, Mice, Transgenic, Nerve Tissue Proteins biosynthesis, Polymerase Chain Reaction, RNA, Messenger biosynthesis, RNA, Messenger genetics, Receptors, Cholinergic biosynthesis, Receptors, Cholinergic genetics, Acetylcholine metabolism, Alzheimer Disease metabolism, Cholesterol metabolism, Frontal Lobe drug effects, Gene Expression Profiling, Nerve Tissue Proteins genetics, Uranyl Nitrate toxicity, Water Pollutants, Chemical toxicity, Water Pollutants, Radioactive toxicity
- Abstract
Some heavy metals, or aluminium, could participate in the development of Alzheimer disease (AD). Depleted uranium (DU), another heavy metal, modulates the cholinergic system and the cholesterol metabolism in the brain of rats, but without neurological disorders. The aim of this study was to determine what happens in organisms exposed to DU that will/are developing the AD. This study was thus performed on a transgenic mouse model for human amyloid precursor protein (APP), the Tg2576 strain. The possible effects of DU through drinking water (20 mg/L) over an 8-month period were analyzed on acetylcholine and cholesterol metabolisms at gene level in the cerebral cortex. The mRNA levels of choline acetyl transferase (ChAT) vesicular acetylcholine transporter (VAChT) and ATP-binding cassette transporter A1 (ABC A1) decreased in control Tg2576 mice in comparison with wild-type mice (respectively -89%, -86% and -44%, p < 0.05). Chronic exposure of Tg2576 mice to DU increased mRNA levels of ChAT (+189%, p < 0.05), VAChT (+120%, p < 0.05) and ABC A1 (+52%, p < 0.05) compared to control Tg2576 mice. Overall, these modifications of acetylcholine and cholesterol metabolisms did not lead to increased disturbances that are specific of AD, suggesting that chronic DU exposure did not worsen the pathology in this experimental model., (Copyright © 2010 Académie des sciences. Published by Elsevier SAS. All rights reserved.)
- Published
- 2011
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