Yuan Xiaoyang, Wang Jing, Chan Hing Man
Department of Biology, University of Ottawa, Ottawa, ON K1N 6N5, Canada.
Regenerative Medicine Program, Ottawa Hospital Research Institute, Ottawa, ON K1H 8L6, Canada.
Toxics. 2018 Oct 10;6(4):61. doi: 10.3390/toxics6040061.
Methylmercury (MeHg) is a ubiquitous environmental pollutant that is known to be neurotoxic, particularly during fetal development. However, the mechanisms responsible for MeHg-induced changes in adult neuronal function, when their exposure occurred primarily during fetal development, are not yet understood. We hypothesized that fetal MeHg exposure could affect neural precursor development leading to long-term neurotoxic effects. Primary cortical precursor cultures obtained from embryonic day 12 were exposed to 0 nM, 0.25 nM, 0.5 nM, 2.5 nM, and 5 nM MeHg for 48 or 72 h. Total Hg accumulated in the harvested cells in a dose-dependent manner. Not all of the concentrations tested in the study affected cell viability. Intriguingly, we observed that cortical precursor exposed to 0.25 nM MeHg showed increased neuronal differentiation, while its proliferation was inhibited. Reduced neuronal differentiation, however, was observed in the higher dose groups. Our results suggest that sub-nanomolar MeHg exposure may deplete the pool of neural precursors by increasing premature neuronal differentiation, which can lead to long-term neurological effects in adulthood as opposed to the higher MeHg doses that cause more immediate toxicity during infant development.
甲基汞（MeHg）是一种普遍存在的环境污染物，已知具有神经毒性，尤其是在胎儿发育期间。然而，对于主要在胎儿发育期间接触甲基汞所导致的成年神经元功能变化的机制，目前尚不清楚。我们推测，胎儿期接触甲基汞可能会影响神经前体细胞的发育，从而导致长期的神经毒性作用。从胚胎第12天获取的原代皮质前体细胞培养物分别用0 nM、0.25 nM、0.5 nM、2.5 nM和5 nM的甲基汞处理48小时或72小时。收获的细胞中总汞的积累呈剂量依赖性。并非研究中测试的所有浓度都会影响细胞活力。有趣的是，我们观察到，暴露于0.25 nM甲基汞的皮质前体细胞神经元分化增加，但其增殖受到抑制。然而，在高剂量组中观察到神经元分化减少。我们的结果表明，亚纳摩尔浓度的甲基汞暴露可能会通过增加神经元过早分化来耗尽神经前体细胞池，这可能导致成年期出现长期神经学影响，而较高剂量的甲基汞则会在婴儿发育期间导致更直接的毒性。
