Slotkin T A, Bartolome J
Neurotoxicology. 1987 Spring;8(1):65-84.
Methylmercury has been designated a "behavioral teratogen" because of its ability to evoke abnormalities in the absence of gross morphological damage to the developing brain. Recent work indicates that exposure to doses of methylmercury associated with neurobehavioral actions causes early alterations in brain ornithine decarboxylase, an enzyme whose activity is related to the coordination of cellular maturation. These effects are followed by regionally-targeted perturbation of cell replication and differentiation, indicated by measurements of nucleic acid and protein synthesis and levels. Neurobehavioral disturbances are associated with postnatal alterations in synaptogenesis and synaptic activity, as exemplified by studies in catecholaminergic pathways. Thus, methylmercury alters neurotransmitter uptake and turnover in presynaptic terminals, as well as development of postsynaptic adrenergic receptor binding sites. These changes result in aberrant signal transmission across the synapse, with consequent effects on synaptic function and ultimately on the communication of trophic developmental signals which ordinarily pass from neuron to target tissue. Although the specific linkages among the various biochemical effects of developmental exposure to methylmercury remain to be elucidated, studies of this type can serve as a model with which to understand the subcellular mechanisms underlying behavioral teratogenesis.
甲基汞已被认定为“行为致畸物”，因为它能够在不造成发育中大脑明显形态损伤的情况下引发异常。最近的研究表明，接触与神经行为作用相关剂量的甲基汞会导致大脑鸟氨酸脱羧酶早期发生改变，该酶的活性与细胞成熟的协调有关。这些影响随后会导致细胞复制和分化的区域靶向性扰动，这可通过核酸和蛋白质合成及水平的测量来表明。神经行为障碍与突触发生和突触活动的产后改变有关，如儿茶酚胺能途径的研究所示。因此，甲基汞会改变突触前末梢的神经递质摄取和周转，以及突触后肾上腺素能受体结合位点的发育。这些变化导致突触间信号传递异常，进而影响突触功能，并最终影响通常从神经元传递到靶组织的营养发育信号的交流。尽管发育性接触甲基汞的各种生化效应之间的具体联系仍有待阐明，但这类研究可作为一个模型，用于理解行为致畸发生的亚细胞机制。
