Neonatal exposure to low doses of diazinon: long-term effects on neural cell development and acetylcholine systems.

Journal Article (Journal Article)

BACKGROUND: The developmental neurotoxicity of organophosphate pesticides involves mechanisms other than their shared property of cholinesterase inhibition. OBJECTIVES: We gave diazinon (DZN) to newborn rats on postnatal days 1-4, using doses (0.5 or 2 mg/kg) spanning the threshold for barely detectable cholinesterase inhibition. METHODS: We then evaluated the lasting effects on indices of neural cell number and size, and on functional markers of acetylcholine (ACh) synapses (choline acetyltransferase, presynaptic high-affinity choline transporter, nicotinic cholinergic receptors) in a variety of brain regions. RESULTS: DZN exposure produced a significant overall increase in cell-packing density in adolescence and adulthood, suggestive of neuronal loss and reactive gliosis; however, some regions (temporal/occipital cortex, striatum) showed evidence of net cell loss, reflecting a greater sensitivity to neurotoxic effects of DZN. Deficits were seen in ACh markers in cerebrocortical areas and the hippocampus, regions enriched in ACh projections. In contrast, there were no significant effects in the midbrain, the major locus for ACh cell bodies. The striatum showed a unique pattern, with robust initial elevations in the ACh markers that regressed in adulthood to normal or subnormal values. CONCLUSIONS: These results indicate that developmental exposures to apparently nontoxic doses of DZN compromise neural cell development and alter ACh synaptic function in adolescence and adulthood. The patterns seen here differ substantially from those seen in earlier work with chlorpyrifos, reinforcing the concept that the various organophosphates have fundamentally different effects on the developmental trajectories of specific neurotransmitter systems, unrelated to their shared action as cholinesterase inhibitors.

Full Text

Duke Authors

Cited Authors

  • Slotkin, TA; Bodwell, BE; Levin, ED; Seidler, FJ

Published Date

  • March 2008

Published In

Volume / Issue

  • 116 / 3

Start / End Page

  • 340 - 348

PubMed ID

  • 18335101

Pubmed Central ID

  • PMC2265026

International Standard Serial Number (ISSN)

  • 0091-6765

Digital Object Identifier (DOI)

  • 10.1289/ehp.11005


  • eng

Conference Location

  • United States