School of Medicine, Medical Research Institute, Neuroscience Research Group, University of Antioquia (UdeA), Calle 62 # 52-59, SIU, Medellin, Colombia.
Biometals. 2011 Dec;24(6):1045-57. doi: 10.1007/s10534-011-9463-0. Epub 2011 May 19.
The biometals iron (Fe), manganese (Mn) and copper (Cu) have been associated to Parkinson's disease (PD) and Parkinsonism. In this work, we report for the first time that acute (15 mM for up to 5 days) or chronic (0.5 mM for up to 15 days) Fe, Mn and Cu exposure significantly reduced life span and locomotor activity (i.e. climbing capabilities) in Drosophila melanogaster. It is shown that the concentration of those biometals dramatically increase in Drosophila's brain acutely or chronically fed with metal. We demonstrate that the metal accumulation in the fly's head is associated with the neurodegeneration of several dopaminergic neuronal clusters. Interestingly, it is found that the PPL2ab DAergic neuronal cluster was erode by the three metals in acute and chronic metal exposure and the PPL3 DAergic cluster was also erode by the three metals but in acute metal exposure only. Furthermore, we found that the chelator desferoxamine, ethylenediaminetetraacetic acid, and D: -penicillamine were able to protect but not rescue D. melanogaster against metal intoxication. Taken together these data suggest that iron, manganese and copper are capable to destroy DAergic neurons in the fly's brain, thereby impairing their movement capabilities. This work provides for the first time metal-induced Parkinson-like symptoms in D. melanogaster. Understanding therefore the effects of biometals in the Drosophila model may provide insights into the toxic effect of metal ions and more effective therapeutic approaches to Parkinsonism.
生物金属铁（Fe）、锰（Mn）和铜（Cu）与帕金森病（PD）和帕金森综合征有关。在这项工作中，我们首次报道急性（15 mM 长达 5 天）或慢性（0.5 mM 长达 15 天）暴露于 Fe、Mn 和 Cu 会显著降低黑腹果蝇的寿命和运动活性（即攀爬能力）。结果表明，急性或慢性喂食金属后，果蝇大脑中的这些生物金属浓度显著增加。我们证明了金属在苍蝇头部的积累与几个多巴胺能神经元簇的神经退行性变有关。有趣的是，发现三种金属均可在急性和慢性金属暴露下侵蚀 PPL2ab DAergic 神经元簇，而三种金属仅在急性金属暴露下侵蚀 PPL3 DAergic 神经元簇。此外，我们发现螯合剂去铁胺、乙二胺四乙酸和 D：-penicillamine 能够保护但不能挽救 D. melanogaster 免受金属中毒。综上所述，这些数据表明铁、锰和铜能够破坏果蝇大脑中的 DAergic 神经元，从而损害其运动能力。本研究首次在 D. melanogaster 中提供了金属诱导的帕金森样症状。因此，了解生物金属在果蝇模型中的作用可能有助于深入了解金属离子的毒性作用，并为帕金森病提供更有效的治疗方法。
