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Neonatal Exposure to Low Doses of Diazinon: Long-Term Effects on Neural Cell Development and Acetylcholine Systems

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 detect...

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Autores principales: Slotkin, Theodore A., Bodwell, Bethany E., Levin, Edward D., Seidler, Frederic J.
Formato: Texto
Lenguaje:English
Publicado: National Institute of Environmental Health Sciences 2008
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2265026/
https://www.ncbi.nlm.nih.gov/pubmed/18335101
http://dx.doi.org/10.1289/ehp.11005
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author Slotkin, Theodore A.
Bodwell, Bethany E.
Levin, Edward D.
Seidler, Frederic J.
author_facet Slotkin, Theodore A.
Bodwell, Bethany E.
Levin, Edward D.
Seidler, Frederic J.
author_sort Slotkin, Theodore A.
collection PubMed
description 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.
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spelling pubmed-22650262008-03-11 Neonatal Exposure to Low Doses of Diazinon: Long-Term Effects on Neural Cell Development and Acetylcholine Systems Slotkin, Theodore A. Bodwell, Bethany E. Levin, Edward D. Seidler, Frederic J. Environ Health Perspect Research 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. National Institute of Environmental Health Sciences 2008-03 2007-12-13 /pmc/articles/PMC2265026/ /pubmed/18335101 http://dx.doi.org/10.1289/ehp.11005 Text en http://creativecommons.org/publicdomain/mark/1.0/ Publication of EHP lies in the public domain and is therefore without copyright. All text from EHP may be reprinted freely. Use of materials published in EHP should be acknowledged (for example, ?Reproduced with permission from Environmental Health Perspectives?); pertinent reference information should be provided for the article from which the material was reproduced. Articles from EHP, especially the News section, may contain photographs or illustrations copyrighted by other commercial organizations or individuals that may not be used without obtaining prior approval from the holder of the copyright.
spellingShingle Research
Slotkin, Theodore A.
Bodwell, Bethany E.
Levin, Edward D.
Seidler, Frederic J.
Neonatal Exposure to Low Doses of Diazinon: Long-Term Effects on Neural Cell Development and Acetylcholine Systems
title Neonatal Exposure to Low Doses of Diazinon: Long-Term Effects on Neural Cell Development and Acetylcholine Systems
title_full Neonatal Exposure to Low Doses of Diazinon: Long-Term Effects on Neural Cell Development and Acetylcholine Systems
title_fullStr Neonatal Exposure to Low Doses of Diazinon: Long-Term Effects on Neural Cell Development and Acetylcholine Systems
title_full_unstemmed Neonatal Exposure to Low Doses of Diazinon: Long-Term Effects on Neural Cell Development and Acetylcholine Systems
title_short Neonatal Exposure to Low Doses of Diazinon: Long-Term Effects on Neural Cell Development and Acetylcholine Systems
title_sort neonatal exposure to low doses of diazinon: long-term effects on neural cell development and acetylcholine systems
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2265026/
https://www.ncbi.nlm.nih.gov/pubmed/18335101
http://dx.doi.org/10.1289/ehp.11005
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