Research in Neurobehavior and Health (NEUROLAB), Universitat Rovira i Virgili, Tarragona, Spain; Department of Psychology and Research Center for Behavior Assessment (CRAMC), Universitat Rovira i Virgili, Tarragona, Spain; Laboratory of Toxicology and Environmental Health, School of Medicine, IISPV, Universitat Rovira i Virgili, Reus, Spain.
Research in Neurobehavior and Health (NEUROLAB), Universitat Rovira i Virgili, Tarragona, Spain; Laboratory of Toxicology and Environmental Health, School of Medicine, IISPV, Universitat Rovira i Virgili, Reus, Spain; Department of Biochemistry and Biotechnology, Universitat Rovira i Virgili, Tarragona, Spain.
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.
迄今为止，我们已经表明载脂蛋白 E (APOE) 多态性可调节毒死蜱 (CPF) 的神经行为和代谢作用，CPF 是一种广泛使用的农药，其残留物可在食物中检测到。我们之前报道过，在接触 CPF 后，APOE3 受试者表现出代谢功能障碍，而 APOE4 受试者则表现出行为改变。在当前的研究中，我们研究了 CPF 的双重暴露对载脂蛋白 E 靶向替换 (TR) 小鼠的社会行为和下丘脑基因表达的影响。雄性 apoE3 和 apoE4-TR 小鼠在出生后第 10-15 天每天接受 0 或 1mg/kg 的 CPF 暴露，然后在成年期（5 个月大）接受 CPF 补充饮食（0 或 2mg/kg/天）15 天。在成年 CPF 暴露期间，监测体重增加和食物摄入量。在成年暴露期结束时，我们在三箱测试中评估了社会行为，以及与社会行为和摄食控制相关的下丘脑神经肽和受体的 mRNA 水平。成年 CPF 暴露普遍增加了食物摄入量，但只有 apoE4 小鼠增加了体重。CPF 暴露后可改善 apoE4 小鼠对社会环境的偏好，而 CPF 暴露后则可改善 apoE3 小鼠对社会环境的偏好。apoE4 小鼠中，成年 CPF 暴露导致厌食肽和与社会行为相关的行为基因表达下降，而神经肽 Y 在 apoE4 小鼠中表达更多。这些结果表明 CPF 暴露产生了食欲和代谢作用，并扩大了社会行为的个体差异，尤其是在 apoE3 小鼠中。
