title: Heavy metal uranium affects the brain cholinergic system in rat following sub-chronic and chronic exposure.
abstract: Uranium is a heavy metal naturally present in the environment that may be chronically ingested by the population. Previous studies have shown that uranium is present in the brain and alters behaviour, notably locomotor activity, sensorimotor ability, sleep/wake cycle and the memory process, but also metabolism of neurotransmitters. The cholinergic system mediates many cognitive systems, including those disturbed after chronic exposure to uranium i.e., spatial memory, sleep/wake cycle and locomotor activity. The objective of this study was to assess whether these disorders follow uranium-induced alteration of the cholinergic system. In comparison with 40 control rats, 40 rats drank 40 mg/L uranyl nitrate for 1.5 or 9 months. Cortex and hippocampus were removed and gene expression and protein level were analysed to determine potential changes in cholinergic receptors and acetylcholine levels. The expression of genes showed various alterations in the two brain areas after short- and long-term exposure. Nevertheless, protein levels of the choline acetyltransferase enzyme (ChAT), the vesicular transporter of acetylcholine (VAChT) and the nicotinic receptor beta2 sub-unit (nAChRbeta2) were unmodified in all cases of the experiment and muscarinic receptor type 1 (m1AChR) protein level was disturbed only after 9 months of exposure in the cortex (-30%). Acetylcholine levels were unchanged in the hippocampus after 1.5 and 9 months, but were decreased in the cortex after 1.5 months only (-22%). Acetylcholinesterase (AChE) activity was also unchanged in the hippocampus but decreased in the cortex after 1.5 and 9 months (-16% and -18%, respectively). Taken together, these data indicate that the cholinergic system is a target of uranium exposure in a structure-dependent and time-dependent manner. These cholinergic alterations could participate in behavioural impairments.
authors.affiliation: Institut de RadioProtection et de Sûreté Nucléaire, Département de la Radioprotection de l'Homme, Service de Radiobiologie et d'Epidémiologie, Laboratoire de Radiotoxicologie Expérimentale, BP 17, F-92262 Fontenay-aux-Roses Cedex, France.
authors.forename: Helene
authors.initials: H
authors.lastname: Bensoussan
authors.forename: Line
authors.initials: L
authors.lastname: Grancolas
authors.forename: Bernadette
authors.initials: B
authors.lastname: Dhieux-Lestaevel
authors.forename: Olivia
authors.initials: O
authors.lastname: Delissen
authors.forename: Claire-Marie
authors.initials: CM
authors.lastname: Vacher
authors.forename: Isabelle
authors.initials: I
authors.lastname: Dublineau
authors.forename: Philippe
authors.initials: P
authors.lastname: Voisin
authors.forename: Patrick
authors.initials: P
authors.lastname: Gourmelon
authors.forename: Mohammed
authors.initials: M
authors.lastname: Taouis
authors.forename: Philippe
authors.initials: P
authors.lastname: Lestaevel
mesh_terms: D000109:Acetylcholine / Q000378:metabolism; D000110:Acetylcholinesterase / Q000378:metabolism; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D002091:Butyrylcholinesterase / Q000378:metabolism; D002540:Cerebral Cortex / Q000187:drug effects* / Q000378:metabolism; D002795:Choline O-Acetyltransferase / Q000378:metabolism; D002799:Cholinergic Fibers / Q000187:drug effects* / Q000378:metabolism; D004785:Environmental Pollutants / Q000633:toxicity*; D005786:Gene Expression Regulation / Q000187:drug effects; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D043643:Receptor, Muscarinic M1 / Q000187:drug effects / Q000378:metabolism; D011978:Receptors, Nicotinic / Q000187:drug effects / Q000378:metabolism; D013997:Time Factors; D014502:Uranyl Nitrate / Q000633:toxicity*; D050494:Vesicular Acetylcholine Transport Proteins / Q000378:metabolism
chemical_list: D000109:Acetylcholine; D000110:Acetylcholinesterase; D002091:Butyrylcholinesterase; D002795:Choline O-Acetyltransferase; D004785:Environmental Pollutants; D012333:RNA, Messenger; D043643:Receptor, Muscarinic M1; D011978:Receptors, Nicotinic; D014502:Uranyl Nitrate; D050494:Vesicular Acetylcholine Transport Proteins; C493461:Slc18a3 protein, rat