Acute and chronic metal exposure impairs locomotion activity in Drosophila melanogaster: a model to study Parkinsonism

Abstract

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.

Negative impact of manganese on honeybee foraging

“…However, our findings are also in contrast to previous studies in mammals [18] and Drosophila [21], which indicated that Mn 2þ exposure leads to dopaminergic neuronal loss, and overall reduced levels of dopamine in the brain. We do not yet understand the main reason for the differences between our current findings and previous reports.…”

Manganese toxicity inDrosophila melanogaster: extension of the life span by resveratrol

“…climbing capabilities) in D. melanogaster. Bonilla-Ramirez, Jimenez-Del-Rio, and Velez-Pardo (2011) found that the concentrations of those metals markedly rose in D. melamogaster brain in acute or chronically fed flies associated with neurodegeneration of several dopaminergic neuronal clusters. Data suggest that Fe, Mn, and Cu are capable of destroying dopaminergic neurons in fly brain, thereby impairing their movement capabilities.…”

“…Therefore, our findings of a decreased locomotor activity in Mn-fed flies (Mn and Mn þ resveratrol groups) might involve the dysfunction of other types of neurons. However, Bonilla-Ramirez, Jimenez-Del-Rio, and Velez-Pardo (2011) reported 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 the life span and motor activity (i.e. climbing capabilities) in D. melanogaster.…”

Manganese Neurotoxicity

“…There are about 200 DAergic neurons in the flies; however, they are responsible for modulating a wide range of behaviors ranging from sleep and locomotion to courtship and learning (Van Swinderen and Andretic 2011). Under chronic Mn exposure, flies show reduced survival, life-span, and reduced locomotor activity, with Mn showing greater toxic effects than iron and copper (Bonilla-Ramirez et al 2011). Mn accumulates in the head of the flies, and the number of DAergic neuronal clusters labeled with green fluorescent protein (GFP) is reduced upon Mn treatment (Bonilla-Ramirez et al 2011).…”

“…Under chronic Mn exposure, flies show reduced survival, life-span, and reduced locomotor activity, with Mn showing greater toxic effects than iron and copper (Bonilla-Ramirez et al 2011). Mn accumulates in the head of the flies, and the number of DAergic neuronal clusters labeled with green fluorescent protein (GFP) is reduced upon Mn treatment (Bonilla-Ramirez et al 2011). This study also showed that Mn-induced DAergic degeneration was associated with impairment in the climbing behavior and mobility shortage analogous to fly PD models.…”