Research in Neurobehavior and Health (NEUROLAB), Universitat Rovira i Virgili, Tarragona, Spain; Department of Biochemistry and Biotechnology, 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 Psychology and Research Center for Behavior Assessment (CRAMC), Universitat Rovira i Virgili, Tarragona, Spain.
Behav Brain Res. 2019 Dec 30;376:112195. doi: 10.1016/j.bbr.2019.112195. Epub 2019 Aug 29.
Chlorpyrifos (CPF) is an extensively used organophosphate pesticide. Exposure to CPF has been related to neurobehavioral disorders, particularly during neurodevelopment. Apolipoprotein E (apoE) is a lipid and cholesterol carrier and a susceptibility factor for cognitive impairment which can influence the response to toxic exposures. The study was aimed at assessing the effects of postnatal exposure to CPF on object recognition memory and its modulation by sex and APOE genotype. Human apoE3 and apoE4 targeted replacement mice and C57BL/6 mice were postnatally exposed to 0 or 1 mg/kg/day of CPF. Recognition memory was evaluated in an Object Recognition Test (ORT). In order to study the contribution of cholinergic and GABAergic neurotransmitter systems to recognition memory, a pharmacological challenge was included. Sex, genotype and postnatal exposure to CPF were key factors throughout the testing period. Specifically, CPF increased exploratory behavior and impaired discrimination performance. We observed that administering scopolamine, a cholinergic antagonist, was detrimental to recognition memory. However, discrimination in C57BL/6 and apoE4 males improved with the administration of the cholinergic agonist rivastigmine, but the same drug worsened retention in apoE4 females. Finally, the GABAergic agonist alprazolam altered performance in a sex- and genotype-dependent manner. Overall, these results suggest complex interactions between sex, APOE genotype and postnatal CPF exposure and indicate a different functioning of both the cholinergic and GABAergic neurotransmitter system between groups.
毒死蜱（CPF）是一种广泛使用的有机磷农药。接触 CPF 与神经行为障碍有关，特别是在神经发育过程中。载脂蛋白 E（apoE）是一种脂质和胆固醇载体，也是认知障碍的易感因素，可能会影响对有毒物质暴露的反应。本研究旨在评估产后暴露于 CPF 对物体识别记忆的影响及其性别和 APOE 基因型的调节作用。人 apoE3 和 apoE4 靶向替换小鼠和 C57BL/6 小鼠在产后暴露于 0 或 1mg/kg/天 CPF。在物体识别测试（ORT）中评估识别记忆。为了研究胆碱能和 GABA 能神经递质系统对识别记忆的贡献，进行了药理学挑战。性别、基因型和产后 CPF 暴露是整个测试期间的关键因素。具体来说，CPF 增加了探索行为并损害了辨别表现。我们观察到，给予胆碱能拮抗剂东莨菪碱对识别记忆有害。然而，C57BL/6 和 apoE4 雄性的辨别能力在给予胆碱能激动剂利斯的明后得到改善，但相同的药物会恶化 apoE4 雌性的保留。最后，GABA 能激动剂阿普唑仑以依赖于性别和基因型的方式改变了性能。总的来说，这些结果表明性别、APOE 基因型和产后 CPF 暴露之间存在复杂的相互作用，并表明两组之间胆碱能和 GABA 能神经递质系统的功能不同。
