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

Eiki Kimura; Ken-ichiro Kubo; Toshihiro Endo; Kazunori Nakajima; Masaki Kakeyama; Chiharu Tohyama

doi:10.2131/jts.42.25

Letter

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

Eiki Kimura, Ken-ichiro Kubo, Toshihiro Endo, Kazunori Nakajima, Masaki Kakeyama, Chiharu Tohyama

Author information

Eiki Kimura
Laboratory of Environmental Health Sciences, Center for Disease Biology and Integrative Medicine, Graduate School of Medicine, The University of Tokyo
Environmental Biology Laboratory, Faculty of Medicine, University of Tsukuba
Ken-ichiro Kubo
Department of Anatomy, Keio University School of Medicine
Toshihiro Endo
Laboratory of Environmental Health Sciences, Center for Disease Biology and Integrative Medicine, Graduate School of Medicine, The University of Tokyo
Department of Neurochemistry, Graduate School of Medicine, The University of Tokyo
Kazunori Nakajima
Department of Anatomy, Keio University School of Medicine
Masaki Kakeyama
Laboratory of Environmental Health Sciences, Center for Disease Biology and Integrative Medicine, Graduate School of Medicine, The University of Tokyo
Laboratory for Systems Neuroscience and Preventive Medicine, Faculty of Human Sciences, Waseda University
Chiharu Tohyama
Laboratory of Environmental Health Sciences, Center for Disease Biology and Integrative Medicine, Graduate School of Medicine, The University of Tokyo
Environmental Biology Laboratory, Faculty of Medicine, University of Tsukuba

Keywords: Aryl hydrocarbon receptor, Developmental neurotoxicity, Hippocampus, In utero electroporation, Neuronal migration

JOURNAL FREE ACCESS

2017 Volume 42 Issue 1 Pages 25-30

DOI https://doi.org/10.2131/jts.42.25

Details

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.

Corresponding author

Register with J-STAGE for free!