title: Transcriptomic effects of depleted uranium on acetylcholine and cholesterol metabolisms in Alzheimer's disease model.
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.
authors.affiliation: Direction de la radioprotection de l'Homme, service de radiobiologie et d'épidémiologie, laboratoire de radiotoxicologie expérimentale, institut de radioprotection et de sûreté nucléaire, Fontenay-aux-Roses, France. philippe.lestaevel@irsn.fr
authors.forename: Philippe
authors.initials: P
authors.lastname: Lestaevel
authors.forename: Hélène
authors.initials: H
authors.lastname: Bensoussan
authors.forename: Radjini
authors.initials: R
authors.lastname: Racine
authors.forename: Fabrice
authors.initials: F
authors.lastname: Airault
authors.forename: Patrick
authors.initials: P
authors.lastname: Gourmelon
authors.forename: Maâmar
authors.initials: M
authors.lastname: Souidi
mesh_terms: D000109:Acetylcholine / Q000378:metabolism*; D000544:Alzheimer Disease / Q000209:etiology / Q000235:genetics / Q000378:metabolism*; D016564:Amyloid beta-Protein Precursor / Q000235:genetics; D000818:Animals; D002352:Carrier Proteins / Q000096:biosynthesis / Q000235:genetics; D002784:Cholesterol / Q000378:metabolism*; D004195:Disease Models, Animal; D004798:Enzymes / Q000096:biosynthesis / Q000235:genetics; D005625:Frontal Lobe / Q000187:drug effects* / Q000378:metabolism; D020869:Gene Expression Profiling; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D009419:Nerve Tissue Proteins / Q000096:biosynthesis / Q000235:genetics*; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D011950:Receptors, Cholinergic / Q000096:biosynthesis / Q000235:genetics; D014502:Uranyl Nitrate / Q000633:toxicity*; D014874:Water Pollutants, Chemical / Q000633:toxicity*; D014875:Water Pollutants, Radioactive / Q000633:toxicity*
chemical_list: C545487:APP protein, human; D016564:Amyloid beta-Protein Precursor; D002352:Carrier Proteins; D004798:Enzymes; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger; D011950:Receptors, Cholinergic; D014874:Water Pollutants, Chemical; D014875:Water Pollutants, Radioactive; D014502:Uranyl Nitrate; D002784:Cholesterol; D000109:Acetylcholine