Kimura Eiki, Ding Yunjie, Tohyama Chiharu
Laboratory of Environmental Health Sciences, Center for Disease Biology and Integrative Medicine, Graduate School of Medicine, The University of Tokyo, Tokyo 113-0033, Japan.
Experimental Biology Laboratory, Faculty of Medicine, University of Tsukuba, Tsukuba 305-8575, Japan.
Sci Rep. 2016 May 20;6:26386. doi: 10.1038/srep26386.
Perinatal exposure to a low level of dioxin, a ubiquitous environmental pollutant, has been shown to induce abnormalities in learning and memory, emotion, and sociality in laboratory animals later in adulthood. However, how aryl hydrocarbon receptor (AhR) signaling activation disrupts the higher brain function remains unclear. Therefore, we studied the possible effects of excessive activation of AhR signaling on neurodevelopmental processes, such as cellular migration and neurite growth, in mice. To this end, we transfected a constitutively active-AhR plasmid into stem cells in the lateral ventricle by in vivo electroporation on postnatal day 1. Transfection was found to induce tangential migration delay and morphological abnormalities in neuronal precursors in the rostral migratory stream at 6 days post-electroporation (dpe) as well as disrupt radial migration in the olfactory bulb and apical and basal dendritic growth of the olfactory interneurons in the granule cell layer at 13 and 20 dpe. These results suggest that the retarded development of interneurons by the excessive AhR signaling may at least in part explain the dioxin-induced abnormal behavioral alterations previously reported in laboratory animals.
围产期暴露于低水平的二噁英（一种普遍存在的环境污染物）已被证明会在成年后期导致实验动物出现学习和记忆、情绪及社交方面的异常。然而，芳烃受体（AhR）信号激活如何破坏高等脑功能仍不清楚。因此，我们研究了AhR信号过度激活对小鼠神经发育过程（如细胞迁移和神经突生长）的可能影响。为此，我们在出生后第1天通过体内电穿孔将组成型活性AhR质粒转染到侧脑室的干细胞中。发现在电穿孔后6天（dpe），转染会导致吻侧迁移流中神经元前体细胞的切向迁移延迟和形态异常，以及在13和20 dpe时破坏嗅球中的径向迁移和颗粒细胞层中嗅觉中间神经元的顶端和基底树突生长。这些结果表明，AhR信号过度激活导致的中间神经元发育迟缓可能至少部分解释了先前在实验动物中报道的二噁英诱导的异常行为改变。
