Methylmercury and nutrition: Adult effects of fetal exposure in experimental models
Methylmercury and nutrition: Adult effects of fetal exposure in experimental models
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DOI：
10.1016/j.neuro.2008.06.007
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发表时间：
2008-09-01
期刊：
影响因子：
3.4
通讯作者：
Reed, Miranda N.
中科院分区：
文献类型：
--
作者：
Newland, M. Christopher;Paletz, Elliott M.;Reed, Miranda N.
人类主要通过食用鱼类或海洋哺乳动物来接触终生发育神经毒剂甲基汞 (MeHg)。鱼类也是重要营养素的极好来源，包括硒和 n-3 多不饱和脂肪酸 (PUFA)，例如二十二碳六烯酸 (DHA)。如果采用适当的暴露措施，发育性甲基汞暴露的实验室模型可用于评估营养物质和甲基汞的作用，并确定潜在的作用机制。当母亲长期接触汞时，即使血液与大脑的比例存在巨大差异，不同物种的每日摄入量与脑汞之间的关系也是一致且有序的。众所周知，低水平的发育性甲基汞会产生感觉缺陷。最近的研究还表明，在妊娠期暴露于大脑中产生低微摩尔浓度的环境之后，就会出现逆向学习任务的坚持。尚未确定该效应的无效应水平。这些暴露不会影响辨别学习、设定转换（超维度转换）或记忆的获取或表现。逆转学习缺陷可能与使用渐进比例强化计划测量的强化物的增强影响有关，这种效果可能导致坚持。还报道了对多巴胺再摄取抑制剂的敏感性增强和对戊巴比妥（一种 GABA(A) 激动剂）的敏感性降低。富含多不饱和脂肪酸或硒的饮食并不能防止甲基汞对逆转学习的影响，但其本身可能会减少表现的变异性，增强注意力或精神运动功能，并可能对这些领域与年龄相关的缺陷提供一定的保护。据推测，在低暴露水平下，奖励处理、多巴胺和 GABA 能神经递质系统以及与选择和坚持相关的皮质区域的改变对发育中的甲基汞特别敏感。甲基汞神经毒性的人体测试应强调这些行为领域。 (C) 2008 Elsevier Inc. 保留所有权利。
Human exposure to the life-span developmental neurotoxicant, methylmercury (MeHg), is primarily via the consumption of fish or marine mammals. Fish are also excellent sources of important nutrients, including selenium and n-3 polyunsaturated fatty acids (PUFAs), such as docosahexaenoic acid (DHA). Laboratory models of developmental MeHg exposure can be employed to assess the roles of nutrients and MeHg and to identify potential mechanisms of action if the appropriate exposure measures are used. When maternal exposure is protracted, relationships between daily intake and brain mercury are consistent and orderly across species, even when large differences in blood:brain ratios exist. It is well established that low-level developmental MeHg produces sensory deficits. Recent studies also show that perseveration in reversal-learning tasks occurs after gestational exposures that produce low micromolar concentrations in the brain. A no-effect level has not been identified for this effect. These exposures do not affect the acquisition or performance of discrimination learning, set shifting (extradimensional shift), or memory. Reversal-learning deficits may be related to enhanced impact of reinforcers as measured using progressive ratio reinforcement schedules, an effect that could result in perseveration. Also reported is enhanced sensitivity to dopamine reuptake inhibitors and diminished sensitivity to pentobarbital, a GABA(A) agonist. Diets rich in PUFAs or selenium do not protect against MeHg's effects on reversal learning but, by themselves, may diminish variability in performance, enhance attention or psychomotor function and may confer some protection against age-related deficits in these areas. It is hypothesized that altered reward processing, dopamine and GABAergic neurotransmitter systems, and cortical regions associated with choice and perseveration are especially sensitive to developmental MeHg at low exposure levels. Human testing for MeHg's neurotoxicity should emphasize these behavioral domains. (C) 2008 Elsevier Inc. All rights reserved.