Acute and chronic metal exposure impairs locomotion activity in Drosophila melanogaster: a model to study Parkinsonism
Acute and chronic metal exposure impairs locomotion activity in Drosophila melanogaster: a model to study Parkinsonism
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DOI：
10.1007/s10534-011-9463-0
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发表时间：
2011-12-01
期刊：
影响因子：
3.5
通讯作者：
Velez-Pardo, Carlos
中科院分区：
文献类型：
--
作者：
Bonilla-Ramirez, Leonardo;Jimenez-Del-Rio, Marlene;Velez-Pardo, Carlos
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，我们报告的第一次，急性（15毫米长达5天）或慢性（0.5毫米长达15天）铁，锰和铜暴露显着降低寿命和运动活动（即攀登能力）在果蝇。结果表明，这些生物金属的浓度显着增加果蝇的大脑急性或慢性喂养金属。我们证明，金属积累在苍蝇的头部与几个多巴胺能神经元簇的神经变性。有趣的是，发现在急性和慢性金属暴露中，PPL 2ab DA能神经元簇被三种金属侵蚀，并且PPL 3 DA能神经元簇也被三种金属侵蚀，但仅在急性金属暴露中。此外，我们还发现去铁胺、乙二胺四乙酸和d-青霉胺对D.抗金属中毒。综合这些数据表明，铁、锰和铜能够破坏果蝇大脑中的DA能神经元，从而损害它们的运动能力。这项工作首次提供了金属诱导的帕金森样症状在D。黑腹果蝇因此，了解生物金属在果蝇模型中的作用可能会提供对金属离子毒性作用的深入了解和更有效的帕金森病治疗方法。
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.