*Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, Ohio 45229.
Division of Neurology (MLC 7044), Cincinnati Children's Research Foundation, Cincinnati, Ohio 45229.
Toxicol Sci. 2019 Jun 1;169(2):511-523. doi: 10.1093/toxsci/kfz067.
Pyrethroids are synthetic insecticides that act acutely on voltage gated sodium channels to prolong channel opening and depolarization. Epidemiological studies find that exposure to pyrethroids are associated with neurological and developmental abnormalities in children. The long-term effects of type II pyrethroids, such as deltamethrin (DLM), on development have received little attention. We exposed Sprague-Dawley rats to DLM by gavage at doses of 0, 0.25, 0.5, and 1.0 mg/kg/day from postnatal day (P) 3-20 in a split-litter design. Following behavioral testing as adults, monoamine levels, release, and mRNA were assessed via high performance liquid chromatography, microdialysis, and qPCR, respectively. Long-term potentiation (LTP) was assessed at P25-35. Developmental DLM exposure resulted in deficits in allocentric and egocentric learning and memory, increased startle reactivity, reduced conditioned contextual freezing, and attenuated MK-801 induced hyperactivity compared with controls. Startle and egocentric learning were preferentially affected in males. Deltamethrin-treated rats exhibited increased CA1 hippocampal LTP, decreased extracellular dopamine release by microdialysis, reduced dopamine D1 receptor mRNA expression in neostriatum, and decreased norepinephrine levels in the hippocampus. The data indicate that neonatal DLM exposure has adverse long-term effects on learning, memory, startle, glutamatergic function, LTP, and norepinephrine.
拟除虫菊酯是一种合成杀虫剂,它通过作用于电压门控钠离子通道而延长通道开放和去极化。流行病学研究发现,接触拟除虫菊酯与儿童的神经和发育异常有关。二型拟除虫菊酯(如氯菊酯)对发育的长期影响尚未得到广泛关注。我们通过灌胃方式,以 0、0.25、0.5 和 1.0mg/kg/天的剂量,从新生后第 3 天至第 20 天,对 Sprague-Dawley 大鼠进行氯菊酯处理,采用分窝设计。成年后进行行为测试,通过高效液相色谱、微透析和 qPCR 分别评估单胺水平、释放和 mRNA。在 P25-35 时评估长时程增强(LTP)。与对照组相比,发育性 DLM 暴露导致非自我中心和自我中心学习和记忆缺陷、惊跳反应增加、条件性上下文冻结减少以及 MK-801 诱导的过度活跃减弱。惊跳和自我中心学习优先受到雄性的影响。氯菊酯处理的大鼠表现出 CA1 海马 LTP 增加、微透析时细胞外多巴胺释放减少、新纹状体多巴胺 D1 受体 mRNA 表达减少以及海马去甲肾上腺素水平降低。这些数据表明,新生儿 DLM 暴露对学习、记忆、惊跳、谷氨酸能功能、LTP 和去甲肾上腺素具有不利的长期影响。