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

被引：44

作者：

Bensoussan, Helene ^{[1
]}

Grancolas, Line ^{[1
]}

Dhieux-Lestaevel, Bernadette ^{[2
]}

Delissen, Olivia ^{[2
]}

Vacher, Claire-Marie ^{[3
]}

Dublineau, Isabelle ^{[1
]}

Voisin, Philippe ^{[1
]}

Gourmelon, Patrick ^{[1
]}

Taouis, Mohammed ^{[3
]}

Lestaevel, Philippe ^{[1
]}

机构：

[1] Inst RadioProtect & Surete Nucl, Dept Radioprotect Homme, Serv Radiobiol & Epidemiol, Lab Radiotoxicol Expt, F-92262 Fontenay Aux Roses, France

[2] Inst RadioProtect & Surete Nucl, Dept Radioprotect Homme, Serv Radiobiol & Epidemiol, Lab Radiotoxicol Expt, F-26702 Pierrelatte, France

[3] Univ Paris 11, Lab Neuroendocrinol Mol Prise Alimentaire, UMR 1197, INRA, F-91405 Orsay, France

来源：

TOXICOLOGY | 2009年 / 261卷 / 1-2期

关键词：

Acetylcholine; Uranium exposure; Cerebral cortex; Hippocampus; CENTRAL-NERVOUS-SYSTEM; DEPLETED URANIUM; SHORT-TERM; ACETYLCHOLINE-RELEASE; CHRONIC CONTAMINATION; SENILE-DEMENTIA; SPATIAL MEMORY; MESSENGER-RNA; RECEPTOR; METABOLISM;

D O I：

10.1016/j.tox.2009.04.054

中图分类号：

R9 [药学];

学科分类号：

100702 [药剂学];

摘要：

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 beta 2 sub-unit (nAChR beta 2) 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. (C) 2009 Elsevier Ireland Ltd. All rights reserved.

引用

页码：59 / 67

页数：9

共 63 条

[1]

Locomotor and sensorimotor performance deficit in rats following exposure to pyridostigmine bromide, DEET, and permethrin, alone and in combination [J].