Perinatal diazinon exposure compromises the development of acetylcholine and serotonin systems.

dc.contributor.author

Slotkin, Theodore A

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Skavicus, Samantha

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Ko, Ashley

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Levin, Edward D

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Seidler, Frederic J

dc.date.accessioned

2023-12-07T00:29:19Z

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2023-12-07T00:29:19Z

dc.date.issued

2019-08

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2023-12-07T00:29:18Z

dc.description.abstract

Organophosphate pesticides are developmental neurotoxicants. We gave diazinon via osmotic minipumps implanted into dams prior to conception, with exposure continued into the second postnatal week, at doses (0.5 or 1 mg/kg/day) that did not produce detectable brain cholinesterase inhibition. We evaluated the impact on acetylcholine (ACh) and serotonin (5-hydroxytryptamine, 5HT) systems in brain regions from adolescence through full adulthood. Diazinon produced deficits in presynaptic ACh activity with regional and sex selectivity: cerebrocortical regions and the hippocampus were affected to a greater extent than were the striatum, midbrain or brainstem, and females were more sensitive than males. Diazinon also reduced nicotinic ACh receptors and 5HT1A receptors, with the same regional and sex preferences. These patterns were similar to those of diazinon given in a much more restricted period (postnatal day 1-4) but were of greater magnitude and consistency; this suggests that the brain is vulnerable to diazinon over a wide developmental window. Diazinon's effects differed from those of the related organophosphate, chlorpyrifos, with regard to regional and sex selectivity, and more importantly, to the effects on receptors: chlorpyrifos upregulates nicotinic ACh receptors and 5HT receptors, effects that compensate for the presynaptic ACh deficits. Diazinon can thus be expected to have worse neurodevelopmental outcomes than chlorpyrifos. Further, the disparities between diazinon and chlorpyrifos indicate the problems of predicting the developmental neurotoxicity of organophosphates based on a single compound, and emphasize the inadequacy of cholinesterase inhibition as an index of safety.

dc.identifier

S0300-483X(19)30186-6

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0300-483X

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1879-3185

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https://hdl.handle.net/10161/29510

dc.language

eng

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Elsevier BV

dc.relation.ispartof

Toxicology

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10.1016/j.tox.2019.152240

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Animals

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Animals, Newborn

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Rats

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Rats, Sprague-Dawley

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Prenatal Exposure Delayed Effects

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Acetylcholine

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Serotonin

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Chlorpyrifos

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Diazinon

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Receptors, Serotonin

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Receptors, Nicotinic

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Cholinesterase Inhibitors

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Insecticides

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Up-Regulation

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Brain Chemistry

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Pregnancy

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Sex Characteristics

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Female

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Male

dc.title

Perinatal diazinon exposure compromises the development of acetylcholine and serotonin systems.

dc.type

Journal article

duke.contributor.orcid

Levin, Edward D|0000-0001-7292-8084|0000-0002-5060-9602

pubs.begin-page

152240

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Duke

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Nicholas School of the Environment

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School of Medicine

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Trinity College of Arts & Sciences

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Basic Science Departments

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Clinical Science Departments

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Institutes and Centers

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Neurobiology

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Pharmacology & Cancer Biology

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Psychiatry & Behavioral Sciences

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Duke Cancer Institute

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Psychology & Neuroscience

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Environmental Sciences and Policy

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Institutes and Provost's Academic Units

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University Institutes and Centers

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Duke Institute for Brain Sciences

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Initiatives

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Duke Science & Society

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Psychiatry & Behavioral Sciences, Behavioral Medicine & Neurosciences

pubs.publication-status

Published

pubs.volume

424

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