Johansson Carolina, Castoldi Anna F, Onishchenko Natalia, Manzo Luigi, Vahter Marie, Ceccatelli Sandra
Division of Toxicology and Neurotoxicology, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
Neurotox Res. 2007 Apr;11(3-4):241-60. doi: 10.1007/BF03033570.
There is an increasing body of evidence on the possible environmental influence on neurodevelopmental and neurodegenerative disorders. Both experimental and epidemiological studies have demonstrated the distinctive susceptibility of the developing brain to environmental factors such as lead, mercury and polychlorinated biphenyls at levels of exposure that have no detectable effects in adults. Methylmercury (MeHg) has long been known to affect neurodevelopment in both humans and experimental animals. Neurobehavioural effects reported include altered motoric function and memory and learning disabilities. In addition, there is evidence from recent experimental neurodevelopmental studies that MeHg can induce depression-like behaviour. Several mechanisms have been suggested from in vivo- and in vitro-studies, such as effects on neurotransmitter systems, induction of oxidative stress and disruption of microtubules and intracellular calcium homeostasis. Recent in vitro data show that very low levels of MeHg can inhibit neuronal differentiation of neural stem cells. This review summarises what is currently known about the neurodevelopmental effects of MeHg and consider the strength of different experimental approaches to study the effects of environmentally relevant exposure in vivo and in vitro.
关于环境因素可能对神经发育障碍和神经退行性疾病产生的影响,现有证据越来越多。实验研究和流行病学研究均已表明,发育中的大脑对铅、汞和多氯联苯等环境因素具有独特的易感性,而这些环境因素在达到对成年人无明显影响的暴露水平时,就会对发育中的大脑产生影响。长期以来,人们已知甲基汞(MeHg)会影响人类和实验动物的神经发育。报告的神经行为影响包括运动功能改变以及记忆和学习障碍。此外,近期实验性神经发育研究的证据表明,甲基汞可诱发类似抑郁的行为。体内和体外研究已提出了多种机制,例如对神经递质系统的影响、氧化应激的诱导以及微管和细胞内钙稳态的破坏。近期的体外数据表明,极低水平的甲基汞就能抑制神经干细胞的神经元分化。本综述总结了目前已知的甲基汞对神经发育的影响,并考量了在体内和体外研究环境相关暴露影响的不同实验方法的优势。