Neurological effects of acute uranium exposure with and without stress
Neurological effects of acute uranium exposure with and without stress
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DOI：
10.1016/j.neuro.2007.05.014
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发表时间：
2007-11-01
期刊：
影响因子：
3.4
通讯作者：
Jortner, B. S.
中科院分区：
文献类型：
--
作者：
Barber, D. S.;Hancock, S. K.;Jortner, B. S.
循环中的铀迅速进入大脑，可能会对神经系统造成不利影响，而神经系统可能会受到压力的调节。在这项研究中，在存在和不存在应激的情况下，检查了大鼠单次肌肉注射 0、0.1、0.3 或 1 mg 铀/kg（醋酸铀酰，UA）的神经学影响。 UA治疗使血清和局部脑铀水平呈时间和剂量依赖性增加。虽然血清水平在第 30 天时恢复到对照水平，但大脑水平仍然升高。施加压力不会影响铀的分布或保留。接触 1 mg U/kg 显着降低步行活动、体重增加、前肢握力和短暂受损的工作记忆。在接触铀之前施加压力可以防止对握力和记忆力的影响。用 1 mg/kg 治疗 3 天后，纹状体多巴胺含量降低了 30%（59 +/- 6 nmol/mg 组织与 41 +/- 5 nmol/mg 组织），但水平在铀暴露后 7 天恢复到对照。通过预先施加压力可以改善对多巴胺的影响。暴露于 UA 不会改变纹状体中 3,4 二羟基苯乙酸 (DOPAC) 的水平或 D2 受体的数量。没有观察到铀或压力对纹状体、海马、小脑或皮质中的 GABA、血清素、去甲肾上腺素或谷胱甘肽 (GSH) 水平产生影响。这些结果表明，单次肌肉注射铀会导致脑部铀水平持续升高，并且剂量高于 0.3 毫克/千克可能会产生不良的神经系统影响。在施用铀之前施加压力可以调节神经系统效应，但该机制并非由于对铀分布的影响。铀暴露还会产生肾毒性，必须考虑到这一点才能准确评估铀对神经功能的影响。 (c) 2007 Elsevier Inc. 保留所有权利。
Circulating uranium rapidly enters the brain and may cause adverse effects on the nervous system that are potentially modulated by stress. In this study, the neurological effects of a single intramuscular injection of 0, 0.1, 0.3, or 1 mg uranium/kg (as uranyl acetate, UA) in rats were examined in the presence and absence of stress. Treatment with UA produced time and dose-dependent increases in serum and regional brain uranium levels. While serum levels returned to control levels by day 30, brain levels remained elevated. Application of stress did not affect the distribution or retention of uranium. Exposure to 1 mg U/kg significantly decreased ambulatory activity, weight gain, forelimb grip strength and transiently impaired working memory. Effects on grip strength and memory were prevented by application of stress prior to uranium exposure. Striatal dopamine content was reduced by 30% 3 days after treatment with 1 mg/kg (59 +/- 6 nmol/mg tissue versus 41 +/- 5 nmol/mg tissue), but levels returned to control 7 days after uranium exposure. The effect on dopamine was ameliorated by prior application of stress. Exposure to UA did not alter 3,4 dihydroxyphenylacetic acid (DOPAC) levels or numbers of D2 receptors in the striatum. No effect of uranium or stress was observed on levels of GABA, serotonin, norepinephrine, or glutathione (GSH) in the striatum, hippocampus, cerebellum, or cortex. These results indicate that single intramuscular exposures to uranium produce sustained elevation of brain uranium levels and at doses above 0.3 mg/kg can have adverse neurological effects. Application of stress prior to uranium administration modulates neurological effects, but the mechanism is not due to effects on uranium distribution. Uranium exposure also produced renal toxicity which must be considered to accurately assess the effects of uranium on neurological function. (c) 2007 Elsevier Inc. All rights reserved.