Despite restrictions on their use, humans are still constantly exposed to
organophosphates (OPs). A huge number of studies have ratified the neurotoxic effects of
chlorpyrifos (CPF) and suggested its association with
neurodegenerative diseases, but data are still scarce. Human
apolipoprotein E (
apoE) plays an important role in
lipid transport and distribution. In humans, the
apoE4 isoform has been linked to an increased risk of
Alzheimer's disease (AD).
ApoE3 is the most prevalent
isoform worldwide, and has been often established as the healthful one. The current study, performed in targeted replacement (TR) adult male mice, aimed to inquire whether genetic variations of the human
apoE respond differently to a chronic dietary challenge with CPF. At four/five months of age, mice carrying
apoE2,
apoE3 or
apoE4 were pair-fed a diet supplemented with CPF at 0 or 2mg/kg
body weight/day for 13weeks.
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.