Developmental neurotoxic effects of chlorpyrifos on acetylcholine and serotonin pathways in an avian model.

Journal Article

The developmental neurotoxicity of organophosphates such as chlorpyrifos (CPF) involves multiple mechanisms that ultimately compromise the function of specific neurotransmitter systems, notably acetylcholine (ACh) and serotonin (5-hydroxytryptamine, 5HT). Studies in mammalian models incorporate both direct effects on brain development and indirect effects mediated through maternal physiology and maternal/neonatal interactions. We examined the effects of CPF in an avian model, which does not share these potential confounds. Chick eggs were injected with CPF (10 or 20 mg/kg) on incubation days 2 and 6 and markers of ACh and 5HT systems were examined at hatching. The higher dose caused a reduction in cholinesterase activity but there was no consistent downregulation of m(2)-muscarinic ACh receptors as would have been expected from ACh hyperstimulation. Both doses evoked significant reductions in the presynaptic high-affinity choline transporter, the rate-limiting factor in ACh biosynthesis, as monitored by binding of hemicholinium-3. Choline acetyltransferase, a constitutive marker for ACh terminals, was unaffected. This suggests that CPF reduces ACh presynaptic activity rather than compromising the development of ACh projections per se. CPF exposure also reduced the expression of cerebrocortical 5HT(1A) receptors. These effects in the chick model recapitulate many of the actions of early gestational CPF exposure in rats, and thus suggest that CPF exerts direct actions on the immature brain to compromise the development of ACh and 5HT pathways.

Full Text

Duke Authors

Cited Authors

  • Slotkin, TA; Seidler, FJ; Ryde, IT; Yanai, J

Published Date

  • September 2008

Published In

Volume / Issue

  • 30 / 5

Start / End Page

  • 433 - 439

PubMed ID

  • 18436430

International Standard Serial Number (ISSN)

  • 0892-0362

Digital Object Identifier (DOI)

  • 10.1016/j.ntt.2008.02.005

Language

  • eng

Conference Location

  • United States