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

Consumption of a High-Fat Diet in Adulthood Ameliorates the Effects of Neonatal Parathion Exposure on Acetylcholine Systems in Rat Brain Regions
http://www.ehponline.org/docs/2009/0800459/abstract.pdf

 

Theodore A. Slotkin, T. Leon Lassiter, Ian T. Ryde, Nicola Wrench, Edward D. Levin, and Frederic J. Seidler

doi: 10.1289/ehp.0800459 (available at http://dx.doi.org/)
Online 3 February 2009
ehponline.org

ABSTRACT

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 in adulthood.
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 as well as 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.