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Consumption of a high-fat diet in adulthood ameliorates the effects of neonatal parathion exposure on acetylcholine systems in rat brain regions.

Publication ,  Journal Article
Slotkin, TA; Lassiter, TL; Ryde, IT; Wrench, N; Levin, ED; Seidler, FJ
Published in: Environ Health Perspect
June 2009

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.

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Published In

Environ Health Perspect

DOI

EISSN

1552-9924

Publication Date

June 2009

Volume

117

Issue

6

Start / End Page

916 / 922

Location

United States

Related Subject Headings

  • Toxicology
  • Receptors, Nicotinic
  • Rats, Sprague-Dawley
  • Rats
  • Protein Binding
  • Pregnancy
  • Parathion
  • Male
  • Insecticides
  • Hemicholinium 3
 

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Slotkin, T. A., Lassiter, T. L., Ryde, I. T., Wrench, N., Levin, E. D., & Seidler, F. J. (2009). Consumption of a high-fat diet in adulthood ameliorates the effects of neonatal parathion exposure on acetylcholine systems in rat brain regions. Environ Health Perspect, 117(6), 916–922. https://doi.org/10.1289/ehp.0800459
Slotkin, Theodore A., T Leon Lassiter, Ian T. Ryde, Nicola Wrench, Edward D. Levin, and Frederic J. Seidler. “Consumption of a high-fat diet in adulthood ameliorates the effects of neonatal parathion exposure on acetylcholine systems in rat brain regions.Environ Health Perspect 117, no. 6 (June 2009): 916–22. https://doi.org/10.1289/ehp.0800459.
Slotkin TA, Lassiter TL, Ryde IT, Wrench N, Levin ED, Seidler FJ. Consumption of a high-fat diet in adulthood ameliorates the effects of neonatal parathion exposure on acetylcholine systems in rat brain regions. Environ Health Perspect. 2009 Jun;117(6):916–22.
Slotkin, Theodore A., et al. “Consumption of a high-fat diet in adulthood ameliorates the effects of neonatal parathion exposure on acetylcholine systems in rat brain regions.Environ Health Perspect, vol. 117, no. 6, June 2009, pp. 916–22. Pubmed, doi:10.1289/ehp.0800459.
Slotkin TA, Lassiter TL, Ryde IT, Wrench N, Levin ED, Seidler FJ. Consumption of a high-fat diet in adulthood ameliorates the effects of neonatal parathion exposure on acetylcholine systems in rat brain regions. Environ Health Perspect. 2009 Jun;117(6):916–922.

Published In

Environ Health Perspect

DOI

EISSN

1552-9924

Publication Date

June 2009

Volume

117

Issue

6

Start / End Page

916 / 922

Location

United States

Related Subject Headings

  • Toxicology
  • Receptors, Nicotinic
  • Rats, Sprague-Dawley
  • Rats
  • Protein Binding
  • Pregnancy
  • Parathion
  • Male
  • Insecticides
  • Hemicholinium 3