Xing X-J, Rui Q, Du M, Wang D-Y
Department of Genetics and Developmental Biology, Key Laboratory of Developmental Genes and Human Disease in Ministry of Education, Southeast University Medical School, Nanjing, China.
Arch Environ Contam Toxicol. 2009 May;56(4):732-41. doi: 10.1007/s00244-009-9307-x. Epub 2009 Mar 15.
In the present study, we investigated the possibly neurotoxic effects of metal (Pb and Hg) exposure at different developmental stages on neuronal loss in the GABAergic nervous system and synaptic functions in the nematode Caenorhabditis elegans. Our data suggest that neuronal survival in GABAergic neurons and cholinergic transmission were relatively stable during development in nematodes. Moreover, neurodegeneration, as shown by the neuronal loss and dorsal/ventral cord gaps, was more severely induced by Pb and Hg exposure at the L1 through L3 larval stages than at the L4 larval and young-adult stages. Similarly, pre- and postsynaptic functions were more severely impaired by Pb and Hg exposure at the L1 through L3 larval stages than at the L4 larval and young-adult stages. Furthermore, both aldicarb and levamisole resistance were significantly correlated with neuronal loss, dorsal cord gap, and ventral cord gap in Pb- and Hg-exposed nematodes, suggesting that neuronal survival was noticeably correlated with synaptic function in metal-exposed nematodes during development. Therefore, younger (L1-L3) larvae show more sensitivity to neurotoxicity of neuronal survival and synaptic function than L4 larvae and young adult nematodes.
在本研究中,我们调查了不同发育阶段金属(铅和汞)暴露对线虫秀丽隐杆线虫γ-氨基丁酸能神经系统中神经元损失及突触功能的潜在神经毒性作用。我们的数据表明,线虫发育过程中γ-氨基丁酸能神经元的神经元存活和胆碱能传递相对稳定。此外,如神经元损失和背/腹索间隙所示,与L4幼虫期和年轻成虫期相比,L1至L3幼虫期暴露于铅和汞更严重地诱导了神经退行性变。同样,与L4幼虫期和年轻成虫期相比,L1至L3幼虫期暴露于铅和汞对突触前和突触后功能的损害更严重。此外,在暴露于铅和汞的线虫中,涕灭威和左旋咪唑抗性均与神经元损失、背索间隙和腹索间隙显著相关,这表明在发育过程中,金属暴露线虫的神经元存活与突触功能明显相关。因此,较年轻的(L1-L3)幼虫比L4幼虫和年轻成虫线虫对神经元存活和突触功能的神经毒性更敏感。