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Neurotoxicity of pesticides

  • Jason R. RichardsonEmail author
  • Vanessa Fitsanakis
  • Remco H. S. Westerink
  • Anumantha G. Kanthasamy
Review

Abstract

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.

Keywords

Pesticide Neurotoxicity Neurodegeneration Organophosphate Pyrethroid Rotenone Pyridaben Mitochondrial Complex I Glyphosate Organochlorine Dieldrin Dichlorodiphenyltrichloroethane Endosulfan Microelectrode array Zebrafish iPSC Paraquat Fungicide 

Abbreviations

2,4-D

2,4-Dichlorophenoxyacetic acid

AChE

Acetylcholinesterase

AD

Alzheimer’s disease

AOP

Adverse outcome pathway

APOE

Apolipoprotein E

BBB

Blood–brain barrier

BHC

Beta-hexachlorocyclohexane

DDE

Dichlorodiphenyldichloroethylene

DDT

Dichlorodiphenyltrichloroethane

DUMBBELS

Diarrhea, urination miosis/muscle weakness, broncorrhea, bradycardia, emesis, lacrimation, salivation/sweating

EPA

US Environmental Protection Agency

FDA

US Food and Drug Administration

GSH

Glutathione

IL1β

Interleukin-1β

IL6

Interleukin 6

iNOS

Inducible nitric oxide synthase

iPSC

Induced pluripotent stem cell

MEA

Microelectrode array

MRI

Magnetic resonance imaging

MN-EBCD

Manganese ethylene-bis-dithiocarbamate

MN/ZN-EBCD

Manganese/Zinc ethylene-bis-dithiocarbamate

MPP+

1-Methyl-4-phylpyridinium

MPTP

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine

NOX2

NADPH oxidase 2

NSC

Neural stem cell

OP

Organophosphate

OPIDN

Organophosphate-induced delayed neuropathy

PD

Parkinson’s disease

PKC

Protein kinase C

SCG2

Secretogranin II

SOD

Superoxide dismutase

SNPc

Substantia nigra pars compacta

SLUD

Salivation, lacrimation, urination, diarrhea

TOCP

Tri-ortho-cresyl phosphate

TNFα

Tumor necrosis factor alpha

UPS

Ubiquitin–proteasome system

WHO

World health organization

Notes

Acknowledgements

JRR was supported by National Institutes of Health Grants R01ES021800, R01ES026057, U01NS108956, and U01NS079249. VF was supported by R15ES027998. AGK was supported by National Institutes of Health R01 Grants ES027245, NS088206, ES026892, and NS10090. The Eugene and Linda Lloyd Endowed Chair and Eminent Scholar and Armbrust Endowment support to AGK are also acknowledged. He also thanks Drs. Adhithiya Charlie, Huajun Jin, and Mr. Gary Zenitsky for their assistance in preparing this manuscript.

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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Department of Environmental Health Sciences, Robert Stempel School of Public Health and Social WorkFlorida International UniversityMiamiUSA
  2. 2.Department of Pharmaceutical SciencesNortheast Ohio Medical UniversityRootstownUSA
  3. 3.Neurotoxicology Research Group, Toxicology Division, Institute for Risk Assessment SciencesUtrecht UniversityUtrechtThe Netherlands
  4. 4.Department of Biomedical Sciences and Iowa Center for Advanced NeurotoxicologyIowa State UniversityAmesUSA

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