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.2009 Jun;117(6):916-22.
doi: 10.1289/ehp.0800459. Epub 2009 Feb 3.

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

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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

Theodore A Slotkin et al. Environ Health Perspect.2009 Jun.

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.

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.

Keywords: acetylcholine; brain development; high-fat diet; organophosphate insecticides; parathion.

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Figures

Figure 1
Figure 1
Effects of neonatal parathion exposure (0.1 or 0.2 mg/kg) and subsequent adult consumption of a high-fat diet on ACh synaptic parameters in the frontal/parietal cortex (A–C) and temporal/occipital cortex (D–F). (A, D) nAChR binding. (B, E) ChAT activity. (C, F) HC3 binding to the presynaptic high-affinity choline transporter. Data represent mean ± SE obtained from six rats per group. ANOVA for each cluster appears within the panels. NS, not significant. *Individual values for which the parathion groups differ from the corresponding diet-matched control.
Figure 2
Figure 2
Effects of neonatal parathion exposure (0.1 or 0.2 mg/kg) and subsequent adult consumption of a high-fat diet on ACh synaptic parameters in the hippocampus (A–C) and striatum (D–F). (A, D) nAChR binding. (B, E) ChAT activity. (C, F) HC3 binding to the presynaptic high-affinity choline transporter. Data represent mean ± SE obtained from six rats per group. ANOVA for each cluster appears within the panels. NS, not significant. *Individual values for which the parathion groups differ from the corresponding diet-matched control.
Figure 3
Figure 3
Effects of neonatal parathion exposure (0.1 or 0.2 mg/kg) and subsequent adult consumption of a high-fat diet on ACh synaptic parameters in the midbrain (A–C) and brainstem (D–F). (A, D) nAChR binding. (B, E) ChAT activity. (C, F) HC3 binding to the presynaptic high-affinity choline transporter. Data represent mean ± SE obtained from six rats per group. ANOVA for each cluster appears within the panels. NS, not significant. *Individual values for which the parathion groups differ from the corresponding diet-matched control.
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References

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