Wang Yu, Liu Wei, Zhang Qian, Zhao Huimin, Quan Xie
Key Laboratory of Industrial Ecology and Environmental Engineering (MOE), School of Environmental Science and Technology, Dalian University of Technology, Dalian 116024, China.
Key Laboratory of Industrial Ecology and Environmental Engineering (MOE), School of Environmental Science and Technology, Dalian University of Technology, Dalian 116024, China.
Food Chem Toxicol. 2015 Feb;76:70-6. doi: 10.1016/j.fct.2014.12.008. Epub 2014 Dec 15.
The present study aims to explore the effects of perfluorooctane sulfonate (PFOS) on cognitive function in developing rats and the underlying mechanism associated with synaptic plasticity. Pregnant Wistar rats were fed with 0, 5, and 15 mg/L of PFOS via drinking water during gestation and lactation. Offspring were exposed to PFOS on prenatal and/or postnatal days by cross-fostering. Spatial learning and memory abilities were tested from postnatal day (PND) 35. We also analyzed the expression pattern of the synaptic plasticity-related genes and proteins in the hippocampus on PND7 and PND35. Results revealed that PFOS exposure reduced the spatial learning and memory abilities of the offspring, particularly of those with prenatal exposure. Meanwhile, protein levels of growth-associated protein-43, neural cell adhesion molecule 1, nerve growth factor, and brain-derived neurotrophic factor decreased on PND35, which are involved in the formation of synaptic plasticity. In contrast, significant increase in gap-43, ncam1, and bdnf genes on the mRNA level was observed on PND7, possibly due to the post-transcriptional mechanism. Results of both behavioral effects and molecular endpoints suggested the high risk of prenatal PFOS exposure. The decline of spatial learning and memory abilities induced by developmental PFOS exposure was closely related to synaptic plasticity.
本研究旨在探讨全氟辛烷磺酸(PFOS)对发育中大鼠认知功能的影响以及与突触可塑性相关的潜在机制。在妊娠和哺乳期,给怀孕的Wistar大鼠通过饮用水分别喂食0、5和15mg/L的PFOS。通过交叉寄养使后代在产前和/或产后接触PFOS。从出生后第35天开始测试空间学习和记忆能力。我们还分析了出生后第7天和第35天海马中与突触可塑性相关的基因和蛋白质的表达模式。结果显示,PFOS暴露降低了后代的空间学习和记忆能力,尤其是产前暴露的后代。同时,在出生后第35天,参与突触可塑性形成的生长相关蛋白43、神经细胞黏附分子1、神经生长因子和脑源性神经营养因子的蛋白质水平下降。相反,在出生后第7天,在mRNA水平上观察到gap-43、ncam1和bdnf基因显著增加,这可能是由于转录后机制。行为效应和分子指标的结果均表明产前PFOS暴露具有高风险。发育性PFOS暴露诱导的空间学习和记忆能力下降与突触可塑性密切相关。