Organophosphorus pesticides – and in particular chlorpyrifos (CPF) – are extensively used worldwide. They mainly exert their toxicity by targeting the cholinergic system. Several studies suggested that the gene coding for apolipoprotein E (apoE), which is a risk factor for several diseases, can also confer different vulnerability to toxic insults. This study was aimed at assessing the long-term effects of postnatal exposure to CPF on learning and memory as well as the expression levels of several genes involved in cholinergic neurotransmission in mice. Both male and female apoE4-TR and C57BL/6 mice were exposed to either 0 or 1 mg/kg/day of CPF by oral gavage using a micropipette on postnatal days 10–15. At 9 months, they were tested in a Morris Water Maze (MWM) and the gene expression in the frontal cortex and hippocampus was evaluated. Our results show that, in males, CPF had an effect on the spatial retention, while in females, it altered the expression levels of nicotinic receptors. Furthermore, apoE4-TR mice performed the worst during the MWM retention and presented low expression levels in a considerable number of cholinergic genes. Taken together, the current results reveal long-term effects in mice nine months after postnatal exposure to CPF, which are modulated by sex and apoE4 genotype.

有机磷农药-尤其是毒死（（CPF）-在世界范围内广泛使用。它们主要通过靶向胆碱能系统发挥其毒性。几项研究表明，编码载脂蛋白E（apoE）的基因（是多种疾病的危险因素）也可以赋予毒性伤害以不同的脆弱性。这项研究旨在评估出生后暴露于CPF对学习和记忆的长期影响以及与小鼠胆碱能神经传递有关的几个基因的表达水平。在出生后第10-15天，使用微量移液管通过口服管饲法将雄性和雌性apoE4-TR和C57BL / 6小鼠暴露于0或1 mg / kg /天的CPF中。在9个月时，在Morris水迷宫（MWM）中对它们进行了测试，并评估了额叶皮层和海马中的基因表达。我们的结果表明，在男性中，CPF对空间保留有影响，而在女性中，CPF改变了烟碱样受体的表达水平。此外，apoE4-TR小鼠在MWM保留期间表现最差，并在相当数量的胆碱能基因中表现出低表达水平。综上所述，目前的结果表明，出生后暴露于CPF后9个月对小鼠产生了长期影响，这受到性别和apoE4基因型的影响。