Transcriptional response of rat cerebrocortical tissue following acute exposure to permethrin or deltamethrin.

Pyrethroids are neurotoxicants that disrupt nervous system function by interacting with a variety of membrane bound ion channels on neuronal plasma membranes. This study is designed to investigate the transcriptional events downstream of pyrethroid-induced disruption of nervous system excitability. Adult, male Long-Evans rats were orally dosed in vivo with a single dose of either permethrin (1, 10, or 100 mg/kg) or deltamethrin (0.3, 1, 3 mg/kg) at levels that produce only modest behaviroal effects in the whole animal (Wolansky et al. 2006). Transcriptional profiles were obtained from frontal cerebrocortical tissue 6 hours after acute exposure. The primary goals were 1) to identify dose-responsive biomarkers of effect for pyrethroids and 2) identify sensitive intracellular signaling or metabolic pathways sensitive to pyrethroid compounds. Keywords: dose response In total 60 samples were analyzed in the present study: vehicle control (n = 12), 1 mg/kg permethrin (n=8), 10 mg/kg permethrin (n = 8), 100 mg/kg permethrin (n = 8), 0.3 mg/kg deltamethrin (n = 8), 1 mg/kg deltamethrin (n = 8), 3 mg/kg deltamethrin (n = 8). Transcriptional profiles for each test subject were obtained independently, without sample pooling. The publication will include an Appendix Table comparing the variability of RMA values (see Sample VALUE columns) to that of GCOS values (see Sample .CHP files).

拟除虫菊酯（Pyrethroids）是一类神经毒素，可通过与神经元质膜上的多种膜结合离子通道相互作用，破坏神经系统正常功能。
本研究旨在探究拟除虫菊酯诱导神经系统兴奋性紊乱后，下游发生的转录调控事件。
选用成年雄性Long-Evans大鼠，通过单次口服方式进行体内染毒：受试药物分别为氯菊酯（permethrin，剂量设置为1、10、100 mg/kg）与溴氰菊酯（deltamethrin，剂量设置为0.3、1、3 mg/kg），染毒剂量仅会在整体动物中引发轻度行为学效应（Wolansky等，2006）。
于急性暴露6小时后，采集大鼠额叶皮层组织，获取其转录组表达谱。
本研究的核心目标有二：其一，筛选可反映拟除虫菊酯暴露效应的剂量依赖性生物标志物；其二，挖掘对拟除虫菊酯类化合物敏感的细胞内信号通路与代谢通路。
关键词：剂量反应
本研究共分析60份样本：溶剂对照组（n=12）、1 mg/kg氯菊酯组（n=8）、10 mg/kg氯菊酯组（n=8）、100 mg/kg氯菊酯组（n=8）、0.3 mg/kg溴氰菊酯组（n=8）、1 mg/kg溴氰菊酯组（n=8）以及3 mg/kg溴氰菊酯组（n=8）。
所有受试个体的转录组谱均独立制备，未进行样本混合。
后续发表的论文将附带附录表格，对比RMA值（详见样本VALUE列）与GCOS值（详见样本.CHP文件）的变异程度。