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Diazinon and parathion diverge in their effects on development of noradrenergic systems.

Publication ,  Journal Article
Slotkin, TA; Skavicus, S; Seidler, FJ
Published in: Brain Res Bull
April 2017

Organophosphate pesticides elicit developmental neurotoxicity through mechanisms over and above their shared property as cholinesterase inhibitors. We compared the consequences of neonatal exposure (postnatal days PN1-4) to diazinon or parathion on development of norepinephrine systems in rat brain, using treatments designed to produce equivalent effects on cholinesterase, straddling the threshold for barely-detectable inhibition. Norepinephrine levels were measured throughout development from the immediate posttreatment period (PN5), to early adolescence (PN30), young adulthood (PN60) and full adulthood (PN100); we assessed multiple brain regions containing all the major noradrenergic synaptic projections. Diazinon elicited a significant overall deficit of norepinephrine, whereas parathion produced a net increase. The effects were not immediately apparent (PN5) but rather emerged over the course of development, indicating that the organophosphate effects represent alteration of the trajectory of development, not just continuance of an initial injury. There were no comparable effects on β-adrenergic receptors, indicating that the presynaptic changes were not an adaptation to an underlying, primary effect on postsynaptic receptor signaling. Because we used the cholinesterase inhibition benchmark, the absolute dose of diazinon was much higher than that of parathion, since the latter is a more potent cholinesterase inhibitor. Our results are consistent with the growing evidence that the various organophosphates can differ in their impact on brain development and that consequently, the cholinesterase benchmark is an inadequate predictor of adverse neurodevelopmental effects.

Duke Scholars

Published In

Brain Res Bull

DOI

EISSN

1873-2747

Publication Date

April 2017

Volume

130

Start / End Page

268 / 273

Location

United States

Related Subject Headings

  • Rats, Sprague-Dawley
  • Parathion
  • Norepinephrine
  • Neurology & Neurosurgery
  • Male
  • Insecticides
  • Female
  • Diazinon
  • Cholinesterase Inhibitors
  • Brain
 

Citation

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Slotkin, T. A., Skavicus, S., & Seidler, F. J. (2017). Diazinon and parathion diverge in their effects on development of noradrenergic systems. Brain Res Bull, 130, 268–273. https://doi.org/10.1016/j.brainresbull.2017.02.004
Slotkin, Theodore A., Samantha Skavicus, and Frederic J. Seidler. “Diazinon and parathion diverge in their effects on development of noradrenergic systems.Brain Res Bull 130 (April 2017): 268–73. https://doi.org/10.1016/j.brainresbull.2017.02.004.
Slotkin TA, Skavicus S, Seidler FJ. Diazinon and parathion diverge in their effects on development of noradrenergic systems. Brain Res Bull. 2017 Apr;130:268–73.
Slotkin, Theodore A., et al. “Diazinon and parathion diverge in their effects on development of noradrenergic systems.Brain Res Bull, vol. 130, Apr. 2017, pp. 268–73. Pubmed, doi:10.1016/j.brainresbull.2017.02.004.
Slotkin TA, Skavicus S, Seidler FJ. Diazinon and parathion diverge in their effects on development of noradrenergic systems. Brain Res Bull. 2017 Apr;130:268–273.
Journal cover image

Published In

Brain Res Bull

DOI

EISSN

1873-2747

Publication Date

April 2017

Volume

130

Start / End Page

268 / 273

Location

United States

Related Subject Headings

  • Rats, Sprague-Dawley
  • Parathion
  • Norepinephrine
  • Neurology & Neurosurgery
  • Male
  • Insecticides
  • Female
  • Diazinon
  • Cholinesterase Inhibitors
  • Brain