Journal
NEUROTOXICOLOGY AND TERATOLOGY
Volume 68, Issue -, Pages 66-71Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.ntt.2018.05.004
Keywords
C. elegans; Mancozeb; Manzate; Mn/Zn ethylene-bis-dithiocarbamate; Neurotransmitters; Neurotransmitter transporters
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Funding
- Edward Burke Endowment for the Natural Sciences
- National Institute of Environmental Health Sciences [R15ES015628]
- NIH Office of Research Infrastructure Programs [P40 OD010440]
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Mancozeb (MZ), an organic-metal fungicide used predominantly on vegetables and fruits, has been linked to neurodegeneration and behavioral disruptions in a variety of organisms, including humans. Both gamma-aminobutyric acid and dopamine neurons appear to be more vulnerable to MZ exposure than other neuronal populations. Based on these observations, we hypothesized that MZ may be differentially transported into these cells through their presynaptic neurotransmitter transporters. To test this, we pretreated Caenorhabditis elegans with transporter antagonists followed by exposure to various concentrations of MZ. Potential neuroprotection was monitored via green fluorescence associated with various neuron populations in transgenic worm strains. Neurodegeneration associated with subacute MZ treatment (30 min) was not altered by transporter antagonist pretreatment. On the other hand, pretreatment with a dopamine transporter antagonist (GBR12909) appeared to protect dopaminergic neurons from chronic (24 h) MZ treatment. These results are consistent with other reports that dopamine transporter levels or activity may modulate toxicity for neurotoxicants.
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