Transport of a manganese/zinc ethylene-bis-dithiocarbamate fungicide may involve pre-synaptic dopaminergic transporters

Montgomery, Kara M.; Corona, Caleb; Frye, Rebekah; Barnett, Reid E.; Bailey, Andy; Fitsanakis, Vanessa A.

doi:10.1016/j.ntt.2018.05.004

“…Studies in C. elegans, however, have shown that the dopaminergic system is one of the targets following either acute or chronic exposures to this fungicide [142,168]. Furthermore, the toxicity appears to be blocked when worms are pretreated with a dopamine transporter antagonist [169], suggesting it may enter dopamine neurons via this presynaptic transporter. Since the neurotoxic mechanism of action of Mn/Zn-EBDC appears to involve oxidative stress [170] and mitochondrial inhibition [171], it is not unreasonable to hypothesize that neurons, among other cell types, would be vulnerable to Mn/Zn-EBDC exposure.…”

Section: Manganese Ethylene-bis-dithiocarbamate (Ebdc)-containing Fun...mentioning

confidence: 99%

Neurotoxicity of pesticides

Richardson

¹

,

Fitsanakis

²

,

Westerink

³

et al. 2019

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Pesticides are unique environmental contaminants that are specifically introduced into the environment to control pests, often by killing them. Although pesticide application serves many important purposes, including protection against crop loss and against vector-borne diseases, there are significant concerns over the potential toxic effects of pesticides to non-target organisms, including humans. In many cases, the molecular target of a pesticide is shared by non-target species, leading to the potential for untoward effects. Here, we review the history of pesticide usage and the neurotoxicity of selected classes of pesticides, including insecticides, herbicides, and fungicides, to humans and experimental animals. Specific emphasis is given to linkages between exposure to pesticides and risk of neurological disease and dysfunction in humans coupled with mechanistic findings in humans and animal models. Finally, we discuss emerging techniques and strategies to improve translation from animal models to humans.

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“…Studies in C. elegans, however, have shown that the dopaminergic system is one of the targets following either acute or chronic exposures to this fungicide [142,168]. Furthermore, the toxicity appears to be blocked when worms are pretreated with a dopamine transporter antagonist [169], suggesting it may enter dopamine neurons via this presynaptic transporter. Since the neurotoxic mechanism of action of Mn/Zn-EBDC appears to involve oxidative stress [170] and mitochondrial inhibition [171], it is not unreasonable to hypothesize that neurons, among other cell types, would be vulnerable to Mn/Zn-EBDC exposure.…”

Section: Manganese Ethylene-bis-dithiocarbamate (Ebdc)-containing Fun...mentioning

confidence: 99%

Neurotoxicity of Pesticides

2020

Advances in Neurotoxicology

0

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Pesticides are unique environmental contaminants that are specifically introduced into the environment to control pests, often by killing them. Although pesticide application serves many important purposes, including protection against crop loss and against vector-borne diseases, there are significant concerns over the potential toxic effects of pesticides to non-target organisms, including humans. In many cases, the molecular target of a pesticide is shared by non-target species, leading to the potential for untoward effects. Here, we review the history of pesticide usage and the neurotoxicity of selected classes of pesticides, including insecticides, herbicides, and fungicides, to humans and experimental animals. Specific emphasis is given to linkages between exposure to pesticides and risk of neurological disease and dysfunction in humans coupled with mechanistic findings in humans and animal models. Finally, we discuss emerging techniques and strategies to improve translation from animal models to humans.

show abstract