Excessive activation of AhR signaling disrupts neuronal migration in the hippocampal CA1 region in the developing mouse

Eiki Kimura, Kenichiro Kubo, Toshihiro Endo, Kazunori Nakajima, Masaki Kakeyama, Chiharu Tohyama

Research output: Contribution to journalLetter

10 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)25-30
Number of pages6
JournalJournal of Toxicological Sciences
Volume42
Issue number1
DOIs
Publication statusPublished - 2017

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Keywords

  • Aryl hydrocarbon receptor
  • Developmental neurotoxicity
  • Hippocampus
  • In utero electroporation
  • Neuronal migration

ASJC Scopus subject areas

  • Toxicology

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