Cargando…

Consumption of a High-Fat Diet in Adulthood Ameliorates the Effects of Neonatal Parathion Exposure on Acetylcholine Systems in Rat Brain Regions

BACKGROUND: Developmental exposure to a wide variety of developmental neurotoxicants, including organophosphate pesticides, evokes late-emerging and persistent abnormalities in acetylcholine (ACh) systems. We are seeking interventions that can ameliorate or reverse the effects later in life. OBJECTI...

Descripción completa

Detalles Bibliográficos
Autores principales: Slotkin, Theodore A., Lassiter, T. Leon, Ryde, Ian T., Wrench, Nicola, Levin, Edward D., Seidler, Frederic J.
Formato: Texto
Lenguaje:English
Publicado: National Institute of Environmental Health Sciences 2009
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2702406/
https://www.ncbi.nlm.nih.gov/pubmed/19590683
http://dx.doi.org/10.1289/ehp.0800459
_version_ 1782168777778003968
author Slotkin, Theodore A.
Lassiter, T. Leon
Ryde, Ian T.
Wrench, Nicola
Levin, Edward D.
Seidler, Frederic J.
author_facet Slotkin, Theodore A.
Lassiter, T. Leon
Ryde, Ian T.
Wrench, Nicola
Levin, Edward D.
Seidler, Frederic J.
author_sort Slotkin, Theodore A.
collection PubMed
description BACKGROUND: Developmental exposure to a wide variety of developmental neurotoxicants, including organophosphate pesticides, evokes late-emerging and persistent abnormalities in acetylcholine (ACh) systems. We are seeking interventions that can ameliorate or reverse the effects later in life. OBJECTIVES: We administered parathion to neonatal rats and then evaluated whether a high-fat diet begun in adulthood could reverse the effects on ACh systems. METHODS: Neonatal rats received parathion on postnatal days 1–4 at 0.1 or 0.2 mg/kg/day, straddling the cholinesterase inhibition threshold. In adulthood, half the animals were switched to a high-fat diet for 8 weeks. We assessed three indices of ACh synaptic function: nicotinic ACh receptor binding, choline acetyltransferase activity, and hemicholinium-3 binding. Determinations were performed in brain regions comprising all the major ACh projections and cell bodies. RESULTS: Neonatal parathion exposure evoked widespread abnormalities in ACh synaptic markers, encompassing effects in brain regions possessing ACh projections and ACh cell bodies. In general, males were affected more than females. Of 17 regional ACh marker abnormalities (10 male, 7 female), 15 were reversed by the high-fat diet. CONCLUSIONS: A high-fat diet reverses neurodevelopmental effects of neonatal parathion exposure on ACh systems. This points to the potential for nonpharmacologic interventions to offset the effects of developmental neurotoxicants. Further, cryptic neurodevelopmental deficits evoked by environmental exposures may thus engender a later preference for a high-fat diet to maintain normal ACh function, ultimately contributing to obesity.
format Text
id pubmed-2702406
institution National Center for Biotechnology Information
language English
publishDate 2009
publisher National Institute of Environmental Health Sciences
record_format MEDLINE/PubMed
spelling pubmed-27024062009-07-09 Consumption of a High-Fat Diet in Adulthood Ameliorates the Effects of Neonatal Parathion Exposure on Acetylcholine Systems in Rat Brain Regions Slotkin, Theodore A. Lassiter, T. Leon Ryde, Ian T. Wrench, Nicola Levin, Edward D. Seidler, Frederic J. Environ Health Perspect Research BACKGROUND: Developmental exposure to a wide variety of developmental neurotoxicants, including organophosphate pesticides, evokes late-emerging and persistent abnormalities in acetylcholine (ACh) systems. We are seeking interventions that can ameliorate or reverse the effects later in life. OBJECTIVES: We administered parathion to neonatal rats and then evaluated whether a high-fat diet begun in adulthood could reverse the effects on ACh systems. METHODS: Neonatal rats received parathion on postnatal days 1–4 at 0.1 or 0.2 mg/kg/day, straddling the cholinesterase inhibition threshold. In adulthood, half the animals were switched to a high-fat diet for 8 weeks. We assessed three indices of ACh synaptic function: nicotinic ACh receptor binding, choline acetyltransferase activity, and hemicholinium-3 binding. Determinations were performed in brain regions comprising all the major ACh projections and cell bodies. RESULTS: Neonatal parathion exposure evoked widespread abnormalities in ACh synaptic markers, encompassing effects in brain regions possessing ACh projections and ACh cell bodies. In general, males were affected more than females. Of 17 regional ACh marker abnormalities (10 male, 7 female), 15 were reversed by the high-fat diet. CONCLUSIONS: A high-fat diet reverses neurodevelopmental effects of neonatal parathion exposure on ACh systems. This points to the potential for nonpharmacologic interventions to offset the effects of developmental neurotoxicants. Further, cryptic neurodevelopmental deficits evoked by environmental exposures may thus engender a later preference for a high-fat diet to maintain normal ACh function, ultimately contributing to obesity. National Institute of Environmental Health Sciences 2009-06 2009-02-03 /pmc/articles/PMC2702406/ /pubmed/19590683 http://dx.doi.org/10.1289/ehp.0800459 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.
Lassiter, T. Leon
Ryde, Ian T.
Wrench, Nicola
Levin, Edward D.
Seidler, Frederic J.
Consumption of a High-Fat Diet in Adulthood Ameliorates the Effects of Neonatal Parathion Exposure on Acetylcholine Systems in Rat Brain Regions
title Consumption of a High-Fat Diet in Adulthood Ameliorates the Effects of Neonatal Parathion Exposure on Acetylcholine Systems in Rat Brain Regions
title_full Consumption of a High-Fat Diet in Adulthood Ameliorates the Effects of Neonatal Parathion Exposure on Acetylcholine Systems in Rat Brain Regions
title_fullStr Consumption of a High-Fat Diet in Adulthood Ameliorates the Effects of Neonatal Parathion Exposure on Acetylcholine Systems in Rat Brain Regions
title_full_unstemmed Consumption of a High-Fat Diet in Adulthood Ameliorates the Effects of Neonatal Parathion Exposure on Acetylcholine Systems in Rat Brain Regions
title_short Consumption of a High-Fat Diet in Adulthood Ameliorates the Effects of Neonatal Parathion Exposure on Acetylcholine Systems in Rat Brain Regions
title_sort consumption of a high-fat diet in adulthood ameliorates the effects of neonatal parathion exposure on acetylcholine systems in rat brain regions
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2702406/
https://www.ncbi.nlm.nih.gov/pubmed/19590683
http://dx.doi.org/10.1289/ehp.0800459
work_keys_str_mv AT slotkintheodorea consumptionofahighfatdietinadulthoodamelioratestheeffectsofneonatalparathionexposureonacetylcholinesystemsinratbrainregions
AT lassitertleon consumptionofahighfatdietinadulthoodamelioratestheeffectsofneonatalparathionexposureonacetylcholinesystemsinratbrainregions
AT rydeiant consumptionofahighfatdietinadulthoodamelioratestheeffectsofneonatalparathionexposureonacetylcholinesystemsinratbrainregions
AT wrenchnicola consumptionofahighfatdietinadulthoodamelioratestheeffectsofneonatalparathionexposureonacetylcholinesystemsinratbrainregions
AT levinedwardd consumptionofahighfatdietinadulthoodamelioratestheeffectsofneonatalparathionexposureonacetylcholinesystemsinratbrainregions
AT seidlerfredericj consumptionofahighfatdietinadulthoodamelioratestheeffectsofneonatalparathionexposureonacetylcholinesystemsinratbrainregions