Exposure to chlorpyrifos at different ages triggers APOE genotype-specific responses in social behavior, body weight and hypothalamic gene expression

Environ Res. 2019 Nov;178:108684. doi: 10.1016/j.envres.2019.108684. Epub 2019 Aug 23.


To date, we have shown that apolipoprotein E (APOE) polymorphisms differentially modulate the neurobehavioral and metabolic effects of chlorpyrifos (CPF), a widely used pesticide, which is detected as residue in food. We previously reported that, after being exposed to CPF, APOE3 subjects exhibit metabolic dysfunctions while APOE4 subjects undergo changes in behavior. In the current study, we investigated the effects of a double exposure to CPF on social behavior and hypothalamic gene expression in apoE-targeted replacement (TR) mice. Male apoE3-and apoE4-TR mice were exposed to CPF at 0 or 1 mg/kg/day on postnatal days 10-15 and then, during adulthood (5 months of age), fed a CPF-supplemented diet (0 or 2 mg/kg/day) for 15 days. During adult exposure to CPF, body weight gain and food intake were monitored. At the end of the adult exposure period, we evaluated social behavior in a three-chamber test, as well as mRNA levels of hypothalamic neuropeptides and receptors related to social behavior and feeding control. Adult CPF exposure increased food intake in general, but only apoE4 mice increased their body weight. Postnatal CPF exposure improved preference for the social contexts in apoE4 mice while adult CPF exposure did the same in apoE3 mice. Anorexigenic-peptide and social-related behavior gene expression decreased as a result of adult CPF exposure in apoE4 mice, and neuropeptide Y was more expressed in apoE4 mice. These results indicate that CPF exposure produces orexigenic and metabolic effects and enlarges individual differences in social behavior, especially in apoE3 mice.

Keywords: APOE genotype; Chlorpyrifos; Feeding control; Gene x environmental factor; Social behavior.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apolipoprotein E4
  • Apolipoproteins E / genetics*
  • Behavior, Animal / drug effects
  • Body Weight / drug effects
  • Chlorpyrifos / toxicity*
  • Gene Expression / drug effects
  • Genotype
  • Hypothalamus / drug effects
  • Hypothalamus / metabolism
  • Insecticides / toxicity*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Social Behavior


  • Apolipoprotein E4
  • Apolipoproteins E
  • Insecticides
  • Chlorpyrifos