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.


OBJECTIVE
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.
Slotkin
Theodore A
TA
Department of Pharmacology & Cancer Biology, Duke University Medical Center, Durham, North Carolina 27710, USA. t.slotkin@duke.edu
Lassiter
T Leon
TL
Ryde
Ian T
IT
Wrench
Nicola
N
Levin
Edward D
ED
Seidler
Frederic J
FJ
D000109:Acetylcholine / Q000378:metabolism*; D000818:Animals; D000831:Animals, Newborn; D001921:Brain / Q000187:drug effects* / Q000378:metabolism*; D002795:Choline O-Acetyltransferase / Q000378:metabolism; D004041:Dietary Fats / Q000627:therapeutic use*; D004789:Enzyme Activation / Q000187:drug effects; D005260:Female; D006426:Hemicholinium 3 / Q000378:metabolism; D007306:Insecticides / Q000633:toxicity; D008297:Male; D010278:Parathion / Q000633:toxicity*; D011247:Pregnancy; D011485:Protein Binding / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D011978:Receptors, Nicotinic / Q000187:drug effects* / Q000378:metabolism
D004041:Dietary Fats; D007306:Insecticides; D011978:Receptors, Nicotinic; D006426:Hemicholinium 3; D010278:Parathion; D002795:Choline O-Acetyltransferase; D000109:Acetylcholine