Department of Sciences and Technologies, University of Sannio, Via Francesco de Sanctis, 82100, Benevento, Italy; Department of Biology and Evolution of Marine Organisms, Stazione Zoologica Anton Dohrn, Villa Comunale, 80121, Naples, Italy.
Department of Biology, University of Ottawa, Marie-Curie Private, Ottawa, ON K1N 9A7, Canada.
Environ Pollut. 2021 Oct 15;287:117151. doi: 10.1016/j.envpol.2021.117151. Epub 2021 Apr 23.
Fuel additive methylcyclopentadienyl manganese tricarbonyl (MMT) is counted as an organic manganese (Mn)-derived compound. The toxic effects of Mn (alone and complexed) on dopaminergic (DA) neurotransmission have been investigated in both cellular and animal models. However, the impact of environmentally relevant Mn exposure on DA neurodevelopment is rather poorly understood. In the present study, the MMT dose of 100 μM (about 5 mg Mn/L) caused up-regulation of DA-related genes in association with cell body swelling and increase in the number of DA neurons of the ventral diencephalon subpopulation DC2. Furthermore, our analysis identified significant brain Mn bioaccumulation and enhancement of total dopamine levels in association with locomotor hyperactivity. Although DA levels were restored at adulthood, we observed a deficit in the acquisition and consolidation of memory. Collectively, these findings suggest that developmental exposure to low-level MMT-derived Mn is responsible for the selective alteration of diencephalic DA neurons and with long-lasting effects on fish explorative behaviour in adulthood.
燃料添加剂甲基环戊二烯基三羰基锰（MMT）被认为是一种有机锰（Mn）衍生化合物。Mn（单独和络合）对多巴胺能（DA）神经递质传递的毒性作用已在细胞和动物模型中进行了研究。然而，环境相关的 Mn 暴露对 DA 神经发育的影响还知之甚少。在本研究中，100 μM 的 MMT 剂量（约 5mg Mn/L）引起了与细胞体肿胀和腹侧间脑亚群 DC2 中 DA 神经元数量增加相关的 DA 相关基因的上调。此外，我们的分析确定了大脑中 Mn 的生物积累显著增加，并与运动过度活跃相关联。尽管 DA 水平在成年期恢复正常，但我们观察到记忆获取和巩固方面存在缺陷。总的来说，这些发现表明，发育期暴露于低水平的 MMT 衍生的 Mn 会导致间脑 DA 神经元的选择性改变，并对成年鱼类的探索行为产生持久影响。
