Neonatal Exposure to PFOS and PFOA in Mice Results in Changes in Proteins which are Important for Neuronal Growth and Synaptogenesis in the Developing Brain
Neonatal Exposure to PFOS and PFOA in Mice Results in Changes in Proteins which are Important for Neuronal Growth and Synaptogenesis in the Developing Brain
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DOI：
10.1093/toxsci/kfp029
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发表时间：
2009-04-01
影响因子：
3.8
通讯作者：
Viberg, Henrik
中科院分区：
文献类型：
--
作者：
Johansson, Niclas;Eriksson, Per;Viberg, Henrik
全氟辛烷磺酸（PFOS）和全氟辛酸（PFOA）属于全氟化合物家族。它们用于工业和消费应用，例如，服装面料、地毯和食品包装。全氟辛烷磺酸和全氟辛酸存在于环境中，并存在于灰尘和母乳中，这意味着新生儿和幼儿在大脑发育过程中可能直接接触到这些物质。最近，我们报告说，全氟辛烷磺酸和全氟辛酸可以导致神经行为缺陷和胆碱能系统的变化，在成年动物，当直接给新生小鼠，从而显示出与其他调查的持久性有机污染物，如二氯-二苯基-三氯乙烷，多氯联苯，多溴联苯醚（PBDEs）的相似性。在最近的研究中，我们还发现，高度溴化的多溴联苯醚会影响新生小鼠大脑中对神经元生长和突触形成至关重要的蛋白质的水平。目前的研究表明，在出生后第10天直接向新生小鼠单次口服剂量为21 μ mol/kg体重的全氟辛烷磺酸或全氟辛酸（11.3或8.70毫克），可显著增加新生小鼠海马体中CaMKII、GAP-43和突触素的水平。两种化合物均显著增加大脑皮层中突触素和tau蛋白的水平，并且PFOA还增加海马中tau蛋白的水平。这些蛋白质对正常的大脑发育很重要，在大脑生长突增的关键时期，这些蛋白质水平的改变可能是早期报道的行为缺陷背后的机制之一。
Perfluorooctane sulfonate (PFOS) and perfluorooctanoic acid (PFOA) belong to the family of perfluorinated compounds. They are used in industrial and consumer applications, e.g., clothing fabrics, carpets, and food packaging. PFOS and PFOA are present in the environment and are found in dust and human milk, which implies that newborns and toddlers can be directly exposed to these agents during brain development. Recently, we reported that PFOS and PFOA can cause neurobehavioral defects and changes in the cholinergic system, in the adult animal, when given directly to neonatal mice, and thereby showing similarities with other investigated persistent organic pollutants, such as dichloro-diphenyl-trichloroethan, polychlorinated biphenyls, and polybrominated diphenyl ethers (PBDEs). In recent studies, we have also seen that highly brominated PBDEs can affect the levels of proteins that are important for neuronal growth and synaptogenesis in the neonatal mouse brain. The present study shows that a single oral dose of either 21 mu mol PFOS or PFOA/kg body weight (11.3 or 8.70 mg), given directly to the neonatal mice on postnatal day 10, significantly increased the levels of CaMKII, GAP-43, and synaptophysin in the hippocampus of the neonatal mouse. Both compounds significantly increased the levels of synaptophysin and tau in cerebral cortex, and PFOA also increased the levels of tau in hippocampus. These proteins are important for normal brain development, and altered levels of these proteins during a critical period of the brain growth spurts could be one of the mechanisms behind earlier reported behavioral defects.