Kimura Eiki, Kubo Ken-Ichiro, Endo Toshihiro, Nakajima Kazunori, Kakeyama Masaki, Tohyama Chiharu
Laboratory of Environmental Health Sciences, Center for Disease Biology and Integrative Medicine, Graduate School of Medicine, The University of Tokyo.
J Toxicol Sci. 2017;42(1):25-30. doi: 10.2131/jts.42.25.
The aryl hydrocarbon receptor (AhR) avidly binds dioxin, a ubiquitous environmental contaminant. Disruption of downstream AhR signaling has been reported to alter neuronal development, and rodent offspring exposed to dioxin during gestation and lactation showed abnormalities in learning and memory, emotion, and social behavior. However, the mechanism behind the disrupted AhR signaling and developmental neurotoxicity induced by xenobiotic ligands remains elusive. Therefore, we studied how excessive AhR activation affects neuronal migration in the hippocampal CA1 region of the developing mouse brain. We transfected constitutively active (CA)-AhR, AhR, or control vector plasmids into neurons via in utero electroporation on gestational day 14 and analyzed neuronal positioning in the hippocampal CA1 region of offspring on postnatal day 14. CA-AhR transfection affected neuronal positioning, whereas no change was observed in AhR-transfected or control hippocampus. These results suggest that constitutively activated AhR signaling disrupts neuronal migration during hippocampal development. Further studies are needed to investigate whether such developmental disruption in the hippocampus leads to the abnormal cognition and behavior of rodent offspring upon maternal exposure to AhR xenobiotic ligands.
芳烃受体（AhR）能与二噁英紧密结合，二噁英是一种普遍存在的环境污染物。据报道，下游AhR信号通路的破坏会改变神经元发育，在妊娠和哺乳期接触二噁英的啮齿动物后代在学习和记忆、情绪及社会行为方面表现出异常。然而，外源性配体诱导的AhR信号通路破坏和发育性神经毒性背后的机制仍不清楚。因此，我们研究了AhR过度激活如何影响发育中小鼠脑海马CA1区的神经元迁移。我们在妊娠第14天通过子宫内电穿孔将组成型激活（CA）-AhR、AhR或对照载体质粒转染到神经元中，并分析出生后第14天后代海马CA1区的神经元定位。CA-AhR转染影响神经元定位，而AhR转染或对照海马体中未观察到变化。这些结果表明，组成型激活的AhR信号通路在海马发育过程中破坏神经元迁移。需要进一步研究来调查海马体中的这种发育破坏是否会导致母体接触AhR外源性配体后啮齿动物后代出现异常认知和行为。
