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Neurobehavioral teratogenicity of sarin in an avian model.

Publication ,  Journal Article
Yanai, J; Pinkas, A; Seidler, FJ; Ryde, IT; Van der Zee, EA; Slotkin, TA
Published in: Neurotoxicol Teratol
2009

Nerve gas organophosphates like sarin are likely to be used in urban terrorism, leading to widespread exposures of pregnant women and young children. Here, we established a model for sarin neurobehavioral teratogenicity in the developing chick so as to explore the consequences of apparently subtoxic sarin exposure and the mechanisms underlying synaptic and behavioral deficits. Chicken eggs were injected with sarin (2, 6 and 12 microg/kg) on incubation days 2 and 6, treatments that did not decrease hatching and did not evoke dysmorphology. After hatching the chicks were tested for filial imprinting and neurochemical markers known to be critical for imprinting. Imprinting was reduced at 2 and 6 microg/kg but not at the highest dose. Acetylcholinesterase and choline acetyltransferase were unaffected but sarin reduced the concentration of the high-affinity choline transporter, the rate-limiting factor in acetylcholine utilization. The concentration of PKC isoforms was assessed in the imprinting-related intermediate part of the medial hyperstriatum ventrale, the region most closely associated with cholinergic function in imprinting behavior. Sarin reduced the concentration of all isoforms (alpha, beta, gamma) with a similar, biphasic dose-response curve to that seen for behavioral performance, a relationship noted in previous work with organophosphate pesticides. Our results indicate that otherwise subtoxic exposures to sarin produce neurodevelopmental deficits; since we utilized a chick model, which is devoid of maternal confounds that are present in mammalian development, the adverse effects of sarin are mediated directly in the developing organism.

Duke Scholars

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Published In

Neurotoxicol Teratol

DOI

EISSN

1872-9738

Publication Date

2009

Volume

31

Issue

6

Start / End Page

406 / 412

Location

United States

Related Subject Headings

  • Toxicology
  • Teratogens
  • Sarin
  • Random Allocation
  • Protein Kinase C
  • Models, Animal
  • Membrane Transport Proteins
  • Male
  • Imprinting, Psychological
  • Female
 

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Yanai, J., Pinkas, A., Seidler, F. J., Ryde, I. T., Van der Zee, E. A., & Slotkin, T. A. (2009). Neurobehavioral teratogenicity of sarin in an avian model. Neurotoxicol Teratol, 31(6), 406–412. https://doi.org/10.1016/j.ntt.2009.07.007
Yanai, Joseph, Adi Pinkas, Frederic J. Seidler, Ian T. Ryde, Eddy A. Van der Zee, and Theodore A. Slotkin. “Neurobehavioral teratogenicity of sarin in an avian model.Neurotoxicol Teratol 31, no. 6 (2009): 406–12. https://doi.org/10.1016/j.ntt.2009.07.007.
Yanai J, Pinkas A, Seidler FJ, Ryde IT, Van der Zee EA, Slotkin TA. Neurobehavioral teratogenicity of sarin in an avian model. Neurotoxicol Teratol. 2009;31(6):406–12.
Yanai, Joseph, et al. “Neurobehavioral teratogenicity of sarin in an avian model.Neurotoxicol Teratol, vol. 31, no. 6, 2009, pp. 406–12. Pubmed, doi:10.1016/j.ntt.2009.07.007.
Yanai J, Pinkas A, Seidler FJ, Ryde IT, Van der Zee EA, Slotkin TA. Neurobehavioral teratogenicity of sarin in an avian model. Neurotoxicol Teratol. 2009;31(6):406–412.
Journal cover image

Published In

Neurotoxicol Teratol

DOI

EISSN

1872-9738

Publication Date

2009

Volume

31

Issue

6

Start / End Page

406 / 412

Location

United States

Related Subject Headings

  • Toxicology
  • Teratogens
  • Sarin
  • Random Allocation
  • Protein Kinase C
  • Models, Animal
  • Membrane Transport Proteins
  • Male
  • Imprinting, Psychological
  • Female