Heavy metal uranium affects the brain cholinergic system in rat following sub-chronic and chronic exposure

Autor: Isabelle Dublineau, Line Grancolas, Claire-Marie Vacher, Philippe Lestaevel, Bernadette Dhieux-Lestaevel, Helene Bensoussan, Philippe Voisin, Mohammed Taouis, Olivia Delissen, Patrick Gourmelon
Přispěvatelé: Institut de RadioProtection et de Sureté Nucléaire, Direction de la Radioprotection de l’Homme, Institut de Radioprotection et de Sûreté Nucléaire (IRSN/PRP-HOM/SRBE), Institut de Radioprotection et de Sûreté Nucléaire (IRSN), Laboratoire de radiotoxicologie expérimentale, Direction de la radioprotection de l'homme, Centre de Neurosciences Paris-Sud (CNPS), Université Paris-Sud - Paris 11 (UP11)-Centre National de la Recherche Scientifique (CNRS)
Jazyk: angličtina
Rok vydání: 2009
Předmět:
Male
medicine.medical_specialty
Time Factors
Vesicular Acetylcholine Transport Proteins
[SDV]Life Sciences [q-bio]
CEREBRAL CORTEX
Hippocampus
Receptors
Nicotinic
Biology
Toxicology
Choline O-Acetyltransferase
ACETYLCHOLINE
Rats
Sprague-Dawley
03 medical and health sciences
chemistry.chemical_compound
0302 clinical medicine
Internal medicine
Muscarinic acetylcholine receptor
medicine
Animals
RNA
Messenger
Neurotransmitter
030304 developmental biology
0303 health sciences
Behavior
Animal
Receptor
Muscarinic M1
URANIUM EXPOSURE
Choline acetyltransferase
Acetylcholinesterase
Rats
Endocrinology
Nicotinic agonist
Cholinergic Fibers
Gene Expression Regulation
chemistry
Butyrylcholinesterase
Uranyl Nitrate
HIPPOCAMPUS
Cholinergic
RAT
Environmental Pollutants
030217 neurology & neurosurgery
Acetylcholine
medicine.drug
Zdroj: Toxicology
Toxicology, Elsevier, 2009, 261 (1-2), pp.59-67. ⟨10.1016/j.tox.2009.04.054⟩
ISSN: 0300-483X
DOI: 10.1016/j.tox.2009.04.054⟩
Popis: International audience; 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.
Databáze: OpenAIRE
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