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Neurotoxicity of pesticides

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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.

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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

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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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Authors and Affiliations

  1. Department of Environmental Health Sciences, Robert Stempel School of Public Health and Social Work, Florida International University, Miami, FL, 33199, USA

    Jason R. Richardson

  2. Department of Pharmaceutical Sciences, Northeast Ohio Medical University, Rootstown, OH, USA

    Vanessa Fitsanakis

  3. Neurotoxicology Research Group, Toxicology Division, Institute for Risk Assessment Sciences, Utrecht University, Utrecht, The Netherlands

    Remco H. S. Westerink

  4. Department of Biomedical Sciences and Iowa Center for Advanced Neurotoxicology, Iowa State University, Ames, IA, USA

    Anumantha G. Kanthasamy

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  4. Anumantha G. Kanthasamy
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Correspondence to Jason R. Richardson.

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Richardson, J.R., Fitsanakis, V., Westerink, R.H.S. et al. Neurotoxicity of pesticides. Acta Neuropathol 138, 343–362 (2019). https://doi.org/10.1007/s00401-019-02033-9

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