Chronic exposure to chlorpyrifos triggered body weight increase and memory impairment depending on human apoE polymorphisms in a targeted replacement mouse model

At four/five months of age, mice carrying apoE2, apoE3 or apoE4 were pair-fed a diet supplemented with CPF at 0 or 2 mg/kg body weight/day for 13 weeks. Cholinergic signs were monitored daily and body weight changes weekly. In the last week of treatment, learning and memory were assessed in a Barnes maze task. Dietary CPF challenge increased body weight only in apoE3 mice. Differences in the acquisition and retention of the Barnes maze were attributed to apoE genetic differences. Our results showed that apoE4 mice performed worse than apoE2 and apoE3 carriers in the acquisition period of the spatial task, and that apoE2 mice had poorer retention than the other two genotypes. On the other hand, CPF increased the search velocity of apoE2 subjects during the acquisition period. Retention was impaired only in CPF-exposed apoE3 mice. These results underline that gene × environment interactions need to be taken into account in epidemiological studies. Given that apoE3, the most common polymorphism in humans, has proved to be the most sensitive to CPF, the potential implications for human health merit serious thought.