Neurobehavioral teratogenicity of sarin in an avian model.

Published

Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • Yanai, J; Pinkas, A; Seidler, FJ; Ryde, IT; Van der Zee, EA; Slotkin, TA

Published Date

  • November 2009

Published In

Volume / Issue

  • 31 / 6

Start / End Page

  • 406 - 412

PubMed ID

  • 19660543

Pubmed Central ID

  • 19660543

Electronic International Standard Serial Number (EISSN)

  • 1872-9738

International Standard Serial Number (ISSN)

  • 0892-0362

Digital Object Identifier (DOI)

  • 10.1016/j.ntt.2009.07.007

Language

  • eng