TY - JOUR
T1 - Neurotoxicity in preclinical models of occupational exposure to organophosphorus compounds
AU - Voorhees, Jaymie R.
AU - Rohlman, Diane S.
AU - Lein, Pamela J.
AU - Pieper, Andrew A.
N1 - Funding Information:
This work was supported by the National Institute for Environmental Health Sciences through the University of Iowa Environmental Health Sciences Research Center (NIEHS/NIH P30 ES005605) to JV and AP, funds to AP, from a donor to the Mary Alice Smith Fund for Neuropsychiatry Research, funds to AP, from the Titan Neurology Research Fund, and by grants from the National Institute of Environmental Health Sciences (R01 ES 016308 and R21 ES026515) to PL and grants from the Fogarty Institute and the National Institute of Environmental Health Sciences (R01 ES 022163) to DR.
Publisher Copyright:
© 2017 Voorhees, Rohlman, Lein and Pieper.
PY - 2017
Y1 - 2017
N2 - Organophosphorus (OPs) compounds are widely used as insecticides, plasticizers, and fuel additives. These compounds potently inhibit acetylcholinesterase (AChE), the enzyme that inactivates acetylcholine at neuronal synapses, and acute exposure to high OP levels can cause cholinergic crisis in humans and animals. Evidence further suggests that repeated exposure to lower OP levels insufficient to cause cholinergic crisis, frequently encountered in the occupational setting, also pose serious risks to people. For example, multiple epidemiological studies have identified associations between occupational OP exposure and neurodegenerative disease, psychiatric illness, and sensorimotor deficits. Rigorous scientific investigation of the basic science mechanisms underlying these epidemiological findings requires valid preclinical models in which tightly-regulated exposure paradigms can be correlated with neurotoxicity. Here, we review the experimental models of occupational OP exposure currently used in the field. We found that animal studies simulating occupational OP exposures do indeed show evidence of neurotoxicity, and that utilization of these models is helping illuminate the mechanisms underlying OP-induced neurological sequelae. Still, further work is necessary to evaluate exposure levels, protection methods, and treatment strategies, which taken together could serve to modify guidelines for improving workplace conditions globally.
AB - Organophosphorus (OPs) compounds are widely used as insecticides, plasticizers, and fuel additives. These compounds potently inhibit acetylcholinesterase (AChE), the enzyme that inactivates acetylcholine at neuronal synapses, and acute exposure to high OP levels can cause cholinergic crisis in humans and animals. Evidence further suggests that repeated exposure to lower OP levels insufficient to cause cholinergic crisis, frequently encountered in the occupational setting, also pose serious risks to people. For example, multiple epidemiological studies have identified associations between occupational OP exposure and neurodegenerative disease, psychiatric illness, and sensorimotor deficits. Rigorous scientific investigation of the basic science mechanisms underlying these epidemiological findings requires valid preclinical models in which tightly-regulated exposure paradigms can be correlated with neurotoxicity. Here, we review the experimental models of occupational OP exposure currently used in the field. We found that animal studies simulating occupational OP exposures do indeed show evidence of neurotoxicity, and that utilization of these models is helping illuminate the mechanisms underlying OP-induced neurological sequelae. Still, further work is necessary to evaluate exposure levels, protection methods, and treatment strategies, which taken together could serve to modify guidelines for improving workplace conditions globally.
KW - Neurotoxicity
KW - Organophosphate ester pesticides
KW - Organophosphate pesticides
KW - Organophosphates
KW - Organophosphorus compounds
UR - http://www.scopus.com/inward/record.url?scp=85011899116&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85011899116&partnerID=8YFLogxK
U2 - 10.3389/fnins.2016.00590
DO - 10.3389/fnins.2016.00590
M3 - Review article
AN - SCOPUS:85011899116
VL - 10
JO - Frontiers in Neuroscience
JF - Frontiers in Neuroscience
SN - 1662-4548
IS - JAN
M1 - 590
ER -