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

    Research output: Contribution to journalLetter

    8 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

    Fingerprint

    Hippocampal CA1 Region
    Aryl Hydrocarbon Receptors
    Chemical activation
    Dioxins
    Xenobiotics
    Rodentia
    Hippocampus
    Ligands
    Maternal Exposure
    Electroporation
    Social Behavior
    Lactation
    Cognition
    Neurons
    Transfection
    Brain
    Emotions
    Plasmids
    Learning
    Impurities

    Keywords

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

    ASJC Scopus subject areas

    • Toxicology

    Cite this

    Excessive activation of AhR signaling disrupts neuronal migration in the hippocampal CA1 region in the developing mouse. / Kimura, Eiki; Kubo, Ken Ichiro; Endo, Toshihiro; Nakajima, Kazunori; Kakeyama, Masaki; Tohyama, Chiharu.

    In: Journal of Toxicological Sciences, Vol. 42, No. 1, 2017, p. 25-30.

    Research output: Contribution to journalLetter

    Kimura, Eiki ; Kubo, Ken Ichiro ; Endo, Toshihiro ; Nakajima, Kazunori ; Kakeyama, Masaki ; Tohyama, Chiharu. / Excessive activation of AhR signaling disrupts neuronal migration in the hippocampal CA1 region in the developing mouse. In: Journal of Toxicological Sciences. 2017 ; Vol. 42, No. 1. pp. 25-30.
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    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.",
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    AU - Kimura, Eiki

    AU - Kubo, Ken Ichiro

    AU - Endo, Toshihiro

    AU - Nakajima, Kazunori

    AU - Kakeyama, Masaki

    AU - Tohyama, Chiharu

    PY - 2017

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    KW - Developmental neurotoxicity

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    KW - In utero electroporation

    KW - Neuronal migration

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