Dipartimento di Biologia, Università di Napoli Federico II, Via Cinthia 21, 80126 Napoli, Italy.
IRGS, Biogem, Via Camporeale, Ariano Irpino, 83031 Avellino, Italy.
Int J Mol Sci. 2017 Nov 20;18(11):2467. doi: 10.3390/ijms18112467.
chlorpyrifos (CPF) is an organophosphate insecticide used to control pests on a variety of food and feed crops. In mammals, maternal exposure to CPF has been reported to induce cerebral cortex thinning, alteration of long-term brain cognitive function, and Parkinson-like symptoms, but the mechanisms of these processes are not fully understood. In this study, we aimed to gain a deeper understanding of the alterations induced in the brains of mice chronically exposed to CPF by dietary intake. For our purpose, we analysed F1 offspring (sacrificed at 3 and 8 months) of , treated in utero and postnatally with 3 different doses of CPF (0.1-1-10 mg/kg/day). Using RT² Profiler PCR Arrays, we evaluated the alterations in the expression of 84 genes associated with neurodegenerative diseases. In the brains of exposed mice, we evidenced a clear dose-response relationship for AChE inhibition and alterations of gene expression. Some of the genes that were steadily down-regulated, such as , , , , and , were directly related to Parkinson's onset. Our experimental results shed light on the possibility that long-term CPF exposure may exert membrane signalling alterations which make brain cells more susceptible to develop neurodegenerative diseases.
毒死蜱(CPF)是一种有机磷杀虫剂,用于控制各种粮食和饲料作物上的害虫。在哺乳动物中,母体暴露于 CPF 已被报道会导致大脑皮层变薄、长期大脑认知功能改变和帕金森样症状,但这些过程的机制尚不完全清楚。在这项研究中,我们旨在更深入地了解通过饮食摄入慢性暴露于 CPF 的小鼠大脑中诱导的变化。为此,我们分析了经宫内和产后用 3 种不同剂量(0.1-1-10mg/kg/天)CPF 处理的 F1 后代(在 3 个月和 8 个月时牺牲)。使用 RT² Profiler PCR 阵列,我们评估了与神经退行性疾病相关的 84 个基因表达的变化。在暴露于 CPF 的小鼠大脑中,我们发现 AChE 抑制和基因表达改变存在明显的剂量反应关系。一些持续下调的基因,如 、 、 、 、 和 ,与帕金森病的发病直接相关。我们的实验结果表明,长期 CPF 暴露可能会引起膜信号转导改变,使脑细胞更容易患上神经退行性疾病。