title: Excessive activation of AhR signaling disrupts neuronal migration in the hippocampal CA1 region in the developing mouse.
abstract: 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.
authors.affiliation: Laboratory of Environmental Health Sciences, Center for Disease Biology and Integrative Medicine, Graduate School of Medicine, The University of Tokyo.
authors.forename: Eiki
authors.initials: E
authors.lastname: Kimura
authors.forename: Ken-Ichiro
authors.initials: KI
authors.lastname: Kubo
authors.forename: Toshihiro
authors.initials: T
authors.lastname: Endo
authors.forename: Kazunori
authors.initials: K
authors.lastname: Nakajima
authors.forename: Masaki
authors.initials: M
authors.lastname: Kakeyama
authors.forename: Chiharu
authors.initials: C
authors.lastname: Tohyama
mesh_terms: D000818:Animals; D056547:CA1 Region, Hippocampal / Q000196:embryology / Q000502:physiology*; D002465:Cell Movement; D018274:Electroporation; D004622:Embryo, Mammalian; D005260:Female; D051379:Mice; D008810:Mice, Inbred C57BL; D009474:Neurons / Q000502:physiology*; D011247:Pregnancy; D018336:Receptors, Aryl Hydrocarbon / Q000235:genetics*; D015398:Signal Transduction
chemical_list: D018336:Receptors, Aryl Hydrocarbon