Racine Radjini, Gueguen Yann, Gourmelon Patrick, Veyssiere Georges, Souidi Maâmar
Institute for Radiological Protection and Nuclear Safety, Radiological Protection and Human Health Division, Radiobiology and Epidemiology Department, Laboratory of Experimental Nuclear Toxicology, BP no 17, F-92262, Fontenay-aux-Roses Cedex, France.
J Mol Neurosci. 2009 Jun;38(2):159-65. doi: 10.1007/s12031-008-9145-8. Epub 2008 Sep 16.
Depleted uranium results from the enrichment of natural uranium for energetic purpose. Its potential dispersion in the environment would set human populations at risk of being contaminated through ingestion. Uranium can build up in the brain and induce behavior disorders. As a major constituent of the myelin sheath, cholesterol is essential to brain function, and several neurological pathologies result from a disruption of cholesterol metabolism. To assess the effect of a chronic contamination with depleted uranium on cerebral cholesterol metabolism, rats were exposed to depleted uranium for 9 months through drinking water at 40 mg/l. The study focuses on gene expression. Cholesterol-catabolizing enzyme CYP46A1 displayed a 39% increase of its messenger RNA (mRNA) level. 3-Hydroxy-3-methylglutamyl CoA synthase gene expression rose from 91%. Concerning cholesterol transport, mRNA levels of scavenger receptor-B1 and adenosine triphosphate-binding cassette transporter A1 increased by 34% and that of apolipoprotein E by 75%. Concerning regulation, gene expression of nuclear receptors peroxisome proliferator-activated receptors alpha and gamma increased by 46% and 36% respectively, whereas that of retinoid-X-receptor decreased by 29%. In conclusion, a chronic internal contamination with depleted uranium does not affect the health status of rats but induces molecular changes in the dynamic equilibrium of the cerebral cholesterol pool.
贫铀是出于能源目的对天然铀进行浓缩后产生的。其在环境中的潜在扩散会使人类面临通过摄入而受到污染的风险。铀会在大脑中蓄积并引发行为紊乱。胆固醇作为髓鞘的主要成分，对大脑功能至关重要，几种神经病理学病症都源于胆固醇代谢紊乱。为评估贫铀慢性污染对脑胆固醇代谢的影响，将大鼠通过饮用每升含40毫克贫铀的水暴露9个月。该研究聚焦于基因表达。胆固醇分解酶CYP46A1的信使核糖核酸（mRNA）水平升高了39%。3-羟基-3-甲基戊二酰辅酶A合酶基因表达从91%上升。关于胆固醇转运，清道夫受体-B1和三磷酸腺苷结合盒转运体A1的mRNA水平分别增加了34%，载脂蛋白E的mRNA水平增加了75%。关于调节，核受体过氧化物酶体增殖物激活受体α和γ的基因表达分别增加了46%和36%，而维甲酸-X-受体的基因表达下降了29%。总之，贫铀的慢性体内污染不会影响大鼠的健康状况，但会诱导脑胆固醇池动态平衡中的分子变化。
