Neurobehavioral teratogenicity of sarin in an avian model

Joseph Yanai*, Adi Pinkas, Frederic J. Seidler, Ian T. Ryde, Eddy A. Van der Zee, Theodore A. Slotkin

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

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Abstract

Nerve gas organophosphates like satin 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 satin (2, 6 and 12 mu g/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 mu g/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 satin are mediated directly in the developing organism. (C) 2009 Elsevier Inc. All rights reserved.

Original languageEnglish
Pages (from-to)406-412
Number of pages7
JournalNeurotoxicology and Teratology
Volume31
Issue number6
DOIs
Publication statusPublished - 2009

Keywords

  • Acetylcholine systems
  • Brain development
  • Chlorpyrifos
  • Cholinesterase
  • Developing chick
  • Organophosphates
  • Serotonin systems
  • AFFINITY CHOLINE UPTAKE
  • CHLORPYRIFOS EXPOSURE
  • NEURAL PROGENITORS
  • POSTNATAL EXPOSURE
  • DEVELOPING RATS
  • BRAIN
  • ACETYLCHOLINE
  • TOXICITY
  • BEHAVIOR
  • DEFICITS

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