Developmental Neurotoxicity of 3,3′,4,4′-Tetrachloroazobenzene with Thyroxine Deficit: Sensitivity of Glia and Dentate Granule Neurons in the Absence of Behavioral Changes
Developmental Neurotoxicity of 3,3′,4,4′-Tetrachloroazobenzene with Thyroxine Deficit: Sensitivity of Glia and Dentate Granule Neurons in the Absence of Behavioral Changes
复制标题
DOI：
10.3390/toxics2030496
复制
发表时间：
2014-09-01
期刊：
影响因子：
4.6
通讯作者：
Mouton, Peter R.
中科院分区：
文献类型：
--
作者：
Harry, G. Jean;Hooth, Michelle J.;Mouton, Peter R.
甲状腺激素（TH）调节神经发育障碍中涉及的生物过程，并可随环境暴露而改变。发育暴露于二恶英样化合物3，3 '，4，4'-四氯偶氮苯（TCAB），诱导血清T4水平的剂量反应缺陷，而3，5，3 '-三碘甲状腺原氨酸或促甲状腺激素没有变化。雌性Sprague-Dawley大鼠在合笼前2周经口灌胃（玉米油，0.1、1.0或10 mg TCAB/kg/天），直至产后第3天，雄性后代从产后第4-21天（PND）开始。PND 21时，高剂量组显示体重增量不足。传统的神经病理学检测没有神经元死亡，髓鞘破坏，或神经胶质增生。在1.0和10 mg/kg/天剂量下，星形胶质细胞显示出更薄且不太复杂的过程。在10 mg/kg/天剂量下，小胶质细胞显示复杂性降低，无偏体视学检测到海马CA 1锥体神经元和齿状颗粒神经元（GC）减少，小脑高尔基体染色显示浦肯野细胞树突状细胞减少。在PND 150时，在1.0 mg/kg/天剂量组中未观察到GC数量和浦肯野细胞分支面积的正常成熟，数量和分支减少表明发育暴露期间开始的效应。在对照组、0.1和1.0 mg/kg/天剂量组中未观察到对断奶后行为评估的影响。海马神经元和神经胶质细胞对TCAB和T4缺陷的敏感性表明，在未来的DNT评估中考虑大脑发育的其他解剖特征提供了支持。
Thyroid hormones (TH) regulate biological processes implicated in neurodevelopmental disorders and can be altered with environmental exposures. Developmental exposure to the dioxin-like compound, 3,3',4,4'-tetrachloroazobenzene (TCAB), induced a dose response deficit in serum T4 levels with no change in 3,5,3'-triiodothyronine or thyroid stimulating hormone. Female Sprague-Dawley rats were orally gavaged (corn oil, 0.1, 1.0, or 10 mg TCAB/kg/day) two weeks prior to cohabitation until post-partum day 3 and male offspring from post-natal day (PND) 4-21. At PND21, the high dose showed a deficit in body weight gain. Conventional neuropathology detected no neuronal death, myelin disruption, or gliosis. Astrocytes displayed thinner and less complex processes at 1.0 and 10 mg/kg/day. At 10 mg/kg/day, microglia showed less complex processes, unbiased stereology detected fewer hippocampal CA1 pyramidal neurons and dentate granule neurons (GC) and Golgi staining of the cerebellum showed diminished Purkinje cell dendritic arbor. At PND150, normal maturation of GC number and Purkinje cell branching area was not observed in the 1.0 mg/kg/day dose group with a diminished number and branching suggestive of effects initiated during developmental exposure. No effects were observed on post-weaning behavioral assessments in control, 0.1 and 1.0 mg/kg/day dose groups. The demonstrated sensitivity of hippocampal neurons and glial cells to TCAB and T4 deficit raises support for considering additional anatomical features of brain development in future DNT evaluations.