Biosca-Brull Judit, Guardia-Escote Laia, Basaure Pia, Cabré Maria, Blanco Jordi, Pérez-Fernández Cristian, Sánchez-Santed Fernando, Domingo José L, Colomina Maria Teresa
Universitat Rovira i Virgili, Research Group in Neurobehavior and Health (NEUROLAB), Tarragona, Spain; Universitat Rovira i Virgili, Department of Psychology and Research Center for Behavior Assessment (CRAMC), Tarragona, Spain; Universitat Rovira i Virgili, Laboratory of Toxicology and Environmental Health, School of Medicine, Reus, Spain.
Universitat Rovira i Virgili, Research Group in Neurobehavior and Health (NEUROLAB), Tarragona, Spain; Universitat Rovira i Virgili, Department of Psychology and Research Center for Behavior Assessment (CRAMC), Tarragona, Spain.
Environ Res. 2023 May 1;224:115461. doi: 10.1016/j.envres.2023.115461. Epub 2023 Feb 14.
The massive use of chlorpyrifos (CPF) has been associated with an increased prevalence of neurodevelopmental disorders. Some previous studies have shown that prenatal, but not postnatal, CPF exposure causes social behavior deficits in mice depending on sex while others have found that in transgenic mice models carrying the human apolipoprotein E (APOE) ε3 and ε4 allele confer different vulnerabilities to either behavioral or metabolic disorders after CPF exposure. This study aims to evaluate, in both sexes, how prenatal CPF exposure and APOE genotype impact on social behavior and its relation to changes in GABAergic and glutamatergic systems. For this purpose, apoE3 and apoE4 transgenic mice were exposed through the diet to 0 or 1 mg/kg/day of CPF, between gestational day 12 and 18. A three-chamber test was used to assess social behavior on postnatal day (PND) 45. Then, mice were sacrificed, and hippocampal samples were analyzed to study the gene expression of GABAergic and glutamatergic elements. Results showed that prenatal exposure to CPF impaired social novelty preference and increased the expression of GABA-A α1 subunit in females of both genotypes. In addition, the expression of GAD1, the ionic cotransporter KCC2 and the GABA-A α2 and α5 subunits were increased in apoE3 mice, whereas CPF treatment only accentuated the expression of GAD1 and KCC2. Nevertheless, future research is needed to evaluate whether the influences detected in the GABAergic system are present and functionally relevant in adults and old mice.
毒死蜱（CPF）的大量使用与神经发育障碍患病率的增加有关。先前的一些研究表明，产前而非产后接触CPF会导致小鼠出现社会行为缺陷，且存在性别差异，而另一些研究发现，在携带人类载脂蛋白E（APOE）ε3和ε4等位基因的转基因小鼠模型中，CPF暴露后对行为或代谢紊乱具有不同的易感性。本研究旨在评估产前CPF暴露和APOE基因型如何影响两性的社会行为及其与GABA能和谷氨酸能系统变化的关系。为此，在妊娠第12天至18天期间，通过饮食让apoE3和apoE4转基因小鼠接触0或1mg/kg/天的CPF。在出生后第45天（PND 45）使用三室试验评估社会行为。然后，处死小鼠，并分析海马样本以研究GABA能和谷氨酸能元件的基因表达。结果表明，产前接触CPF会损害社会新奇偏好，并增加两种基因型雌性小鼠中GABA-A α1亚基的表达。此外，apoE3小鼠中GAD1、离子共转运体KCC2以及GABA-A α2和α5亚基的表达增加，而CPF处理仅加剧了GAD1和KCC2的表达。然而，需要进一步的研究来评估在GABA能系统中检测到的影响在成年和老年小鼠中是否存在以及是否具有功能相关性。
