Royland Joyce E, Wu Jinfang, Zawia Nasser H, Kodavanti Prasada Rao S
Neurotoxicology Divisions, NHEERL, ORD, U.S. Environmental Protection Agency, Research Triangle Park, NC 27711, USA.
Toxicol Appl Pharmacol. 2008 Sep 1;231(2):165-78. doi: 10.1016/j.taap.2008.04.022. Epub 2008 May 6.
The developmental consequences of exposure to the polychlorinated biphenyls (PCBs) have been widely studied, making PCBs a unique model to understand issues related to environmental mixture of persistent chemicals. PCB exposure in humans adversely affects neurocognitive development, causes psychomotor difficulties, and contributes to attention deficits in children, all of which seem to be associated with altered patterns of neuronal connectivity. In the present study, we examined gene expression profiles in the rat nervous system following PCB developmental exposure. Pregnant rats (Long-Evans) were dosed perinatally with 0 or 6 mg/kg/day of Aroclor 1254 from gestation day 6 through postnatal day (PND) 21. Gene expression in cerebellum and hippocampus from PND7 and PND14 animals was analyzed with an emphasis on developmental aspects. Changes in gene expression (> or =1.5 fold) in control animals identified normal developmental changes. These basal levels of expression were compared to data from Aroclor 1254-treated animals to determine the impact of gestational PCB exposure on developmental parameters. The results indicate that the expression of a number of developmental genes related to cell cycle, synaptic function, cell maintenance, and neurogenesis is significantly altered from PND7 to PND14. Aroclor 1254 treatment appears to dampen the overall growth-related gene expression levels in both regions with the effect being more pronounced in the cerebellum. Functional analysis suggests that Aroclor 1254 delays maturation of the developing nervous system, with the consequences dependent on the ontological state of the brain area and the functional role of the individual gene. Such changes may underlie learning and memory deficits observed in PCB exposed animals and humans.
多氯联苯（PCBs）暴露对发育的影响已得到广泛研究，这使PCBs成为理解与持久性化学物质环境混合物相关问题的独特模型。人类接触PCBs会对神经认知发育产生不利影响，导致精神运动障碍，并导致儿童注意力缺陷，所有这些似乎都与神经元连接模式的改变有关。在本研究中，我们检测了发育过程中暴露于PCBs的大鼠神经系统中的基因表达谱。怀孕的大鼠（Long-Evans品系）在妊娠第6天至出生后第21天（PND）期间，每天按0或6mg/kg的剂量给予Aroclor 1254。重点分析了PND7和PND14动物小脑和海马中的基因表达，以研究发育方面的变化。通过对照动物基因表达的变化（≥1.5倍）确定正常的发育变化。将这些基础表达水平与Aroclor 1254处理动物的数据进行比较，以确定孕期PCB暴露对发育参数的影响。结果表明，从PND7到PND14，许多与细胞周期、突触功能、细胞维持和神经发生相关的发育基因的表达发生了显著改变。Aroclor 1254处理似乎抑制了这两个区域中与整体生长相关的基因表达水平，在小脑中这种影响更为明显。功能分析表明，Aroclor 1254会延迟发育中神经系统的成熟，其后果取决于脑区的本体状态和单个基因的功能作用。这些变化可能是在接触PCB的动物和人类中观察到的学习和记忆缺陷的基础。
