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

Publication ,  Journal Article
Slotkin, TA; Skavicus, S; Ko, A; Levin, ED; Seidler, FJ
Published in: Toxicology
August 1, 2019

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.

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Published In

Toxicology

DOI

EISSN

1879-3185

Publication Date

August 1, 2019

Volume

424

Start / End Page

152240

Location

Ireland

Related Subject Headings

  • Up-Regulation
  • Toxicology
  • Sex Characteristics
  • Serotonin
  • Receptors, Serotonin
  • Receptors, Nicotinic
  • Rats, Sprague-Dawley
  • Rats
  • Prenatal Exposure Delayed Effects
  • Pregnancy
 

Citation

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Slotkin, T. A., Skavicus, S., Ko, A., Levin, E. D., & Seidler, F. J. (2019). Perinatal diazinon exposure compromises the development of acetylcholine and serotonin systems. Toxicology, 424, 152240. https://doi.org/10.1016/j.tox.2019.152240
Slotkin, Theodore A., Samantha Skavicus, Ashley Ko, Edward D. Levin, and Frederic J. Seidler. “Perinatal diazinon exposure compromises the development of acetylcholine and serotonin systems.Toxicology 424 (August 1, 2019): 152240. https://doi.org/10.1016/j.tox.2019.152240.
Slotkin TA, Skavicus S, Ko A, Levin ED, Seidler FJ. Perinatal diazinon exposure compromises the development of acetylcholine and serotonin systems. Toxicology. 2019 Aug 1;424:152240.
Slotkin, Theodore A., et al. “Perinatal diazinon exposure compromises the development of acetylcholine and serotonin systems.Toxicology, vol. 424, Aug. 2019, p. 152240. Pubmed, doi:10.1016/j.tox.2019.152240.
Slotkin TA, Skavicus S, Ko A, Levin ED, Seidler FJ. Perinatal diazinon exposure compromises the development of acetylcholine and serotonin systems. Toxicology. 2019 Aug 1;424:152240.
Journal cover image

Published In

Toxicology

DOI

EISSN

1879-3185

Publication Date

August 1, 2019

Volume

424

Start / End Page

152240

Location

Ireland

Related Subject Headings

  • Up-Regulation
  • Toxicology
  • Sex Characteristics
  • Serotonin
  • Receptors, Serotonin
  • Receptors, Nicotinic
  • Rats, Sprague-Dawley
  • Rats
  • Prenatal Exposure Delayed Effects
  • Pregnancy