The Ross Laboratory for Studies in Neural Birth Defects, Department of Medical Neurobiology, Institute for Medical Research-Israel-Canada, The Hebrew University, Hadassah Medical School, Box 12272, 91120 Jerusalem, Israel.
Neurotoxicol Teratol. 2010 Mar-Apr;32(2):182-6. doi: 10.1016/j.ntt.2009.11.004. Epub 2009 Nov 27.
Perfluorinated alkyls are widely-used agents that accumulate in ecosystems and organisms because of their slow rate of degradation. There is increasing concern that these agents may be developmental neurotoxicants and the present study was designed to develop an avian model for the neurobehavioral teratogenicity of perfluorooctanoic acid (PFOA) and perfluorooctane sulfonate (PFOS). Fertilized chicken eggs were injected with 5 or 10mg/kg of either compound on incubation day 0. On the day of hatching, imprinting behavior was impaired by both compounds. We then explored underlying mechanisms involving the targeting of protein kinase C (PKC) isoforms (alpha, beta, gamma) in the intermedial part of the hyperstriatum ventrale, the region most closely associated with imprinting. With PFOA exposure, cytosolic PKC concentrations were significantly elevated for all three isoforms; despite the overall increase in PKC expression, membrane-associated PKC was unaffected, indicating a defect in PKC translocation. In contrast, PFOS exposure evoked a significant decrease in cytosolic PKC, primarily for the beta and gamma isoforms, but again without a corresponding change in membrane-associated enzyme; this likely partial, compensatory increases in translocation to offset the net PKC deficiency. Our studies indicate that perfluorinated alkyls are indeed developmental neurotoxicants that affect posthatch cognitive performance but that the underlying synaptic mechanisms may differ substantially among the various members of this class of compounds, setting the stage for disparate outcomes later in life.
全氟烷基物质由于其缓慢的降解速度而在生态系统和生物体内广泛积累，被认为是一种蓄积性神经毒物。目前越来越多的研究表明全氟辛烷磺酸（PFOS）和全氟辛酸（PFOA）可能具有发育神经毒性。本研究旨在建立一种用于研究全氟辛烷磺酸和全氟辛酸神经行为致畸性的禽类模型。受精鸡蛋在孵化的第 0 天注射 5 或 10mg/kg 的化合物。在孵化当天，两种化合物都损害了印记行为。我们随后探索了涉及蛋白激酶 C（PKC）同工型（alpha、beta、gamma）在中隔腹侧神经核（与印记最密切相关的区域）靶向的潜在机制。在 PFOA 暴露下，所有三种同工型的细胞质 PKC 浓度均显著升高；尽管 PKC 表达总体增加，但膜结合 PKC 不受影响，表明 PKC 易位存在缺陷。相比之下，PFOS 暴露会导致细胞质 PKC 显著减少，主要是 beta 和 gamma 同工型，但膜结合酶没有相应变化；这可能是部分补偿性增加易位以抵消 PKC 缺乏的净效应。我们的研究表明，全氟烷基物质确实是发育神经毒物，会影响孵化后的认知表现，但在该类化合物的各种成员中，潜在的突触机制可能存在显著差异，为日后产生不同的结果奠定了基础。
