Methylmercury (MeHg) is an environmental toxicant with detrimental effects on the developing brain and adult nervous system. The main mechanisms identified include oxidative stress, changes in intracellular calcium, mitochondrial changes, inhibition of glutamate uptake, of protein synthesis and disruption of microtubules. However, little is known about mechanisms of protection against MeHg neurotoxicity. We found that resveratrol (10 μM) and ascorbic acid (200 μM) protected MeHg-induced cell death in primary cultures of cortical neurons. In this work, we aimed at finding additional targets that may be related to MeHg mode of action in cell toxicity with special emphasis in cell protection. We wonder whether neurotransmitters may affect the MeHg effects on neuronal death. Our findings show that neurons exposed to low MeHg concentrations exhibit less mortality if co-exposed to 10 μM dopamine (DA). However, DA metabolites, HVA (homovanillic acid) and DOPAC (3,4-dihydroxyphenylacetic acid) are not responsible for such protection. Furthermore, both DA D1 and D2 receptors agonists showed a protective effect against MeHg toxicity. It is striking though that DA receptor antagonists SKF83566 (10 μM) and haloperidol (10 μM) did not inhibit DA protection against MeHg. In addition, the protective effect of 10 μM DA against MeHg-induced toxicity was not affected by additional organochlorine pollutants exposure. Our results also demonstrate that cells exposed to MeHg in presence of 100 μM acetylcholine (ACh), show an increase in cell mortality at the “threshold value” of 100 nM MeHg. Finally, norepinephrine (10 μM) and serotonin (20 μM) also had an effect on cell protection. Altogether, we propose to further investigate the additional mechanisms that may be playing an important role in MeHg-induced cytotoxicity.

甲基汞（MeHg）是一种环境毒物，会对发育中的大脑和成人神经系统产生有害影响。确定的主要机制包括氧化应激，细胞内钙的变化，线粒体的变化，谷氨酸的吸收抑制，蛋白质合成和微管破坏。然而，关于针对MeHg神经毒性的保护机制知之甚少。我们发现白藜芦醇（10μM）和抗坏血酸（200μM）保护了皮质神经元原代培养物中MeHg诱导的细胞死亡。在这项工作中，我们旨在寻找可能与MeHg细胞毒性作用方式有关的其他靶标，并特别强调细胞保护。我们想知道神经递质是否会影响甲基汞对神经元死亡的影响。我们的发现表明，与10μM多巴胺（DA）共同暴露于低MeHg浓度的神经元死亡率更低。但是，DA代谢产物，HVA（高香草酸）和DOPAC（3,4-二羟基苯基乙酸）对这种保护作用不负责任。此外，DA D1和D2受体激动剂均显示出对MeHg毒性的保护作用。令人惊讶的是，DA受体拮抗剂SKF83566（10μM）和氟哌啶醇（10μM）并未抑制DA对MeHg的保护作用。此外，10μMDA对MeHg诱导的毒性的保护作用不受其他有机氯污染物暴露的影响。我们的结果还表明，在100μM乙酰胆碱（ACh）存在下暴露于MeHg的细胞在“阈值”为100 nM MeHg时显示出细胞死亡率的增加。最后，去甲肾上腺素（10μM）和血清素（20μM）也对细胞保护有影响。总之，我们建议进一步研究可能在MeHg诱导的细胞毒性中起重要作用的其他机制。