title: Developmental origin of abnormal dendritic growth in the mouse brain induced by in utero disruption of aryl hydrocarbon receptor signaling.
abstract: Increased prevalence of mental disorders cannot be solely attributed to genetic factors and is considered at least partly attributable to chemical exposure. Among various environmental chemicals, in utero and lactational dioxin exposure has been extensively studied and is known to induce higher brain function abnormalities in both humans and laboratory animals. However, how the perinatal dioxin exposure affects neuromorphological alterations has remained largely unknown. Therefore, in this study, we initially studied whether and how the over-expression of aryl hydrocarbon receptor (AhR), a dioxin receptor, would affect the dendritic growth in the hippocampus of the developing brain. Transfecting a constitutively active AhR plasmid into the hippocampus via in utero electroporation on gestational day (GD) 14 induced abnormal dendritic branch growth. Further, we observed that 14-day-old mice born to dams administered with 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD; dose: 0, 0.6, or 3.0 μg/kg) on GD 12.5 exhibited disrupted dendritic branch growth in both the hippocampus and amygdala. Finally, we observed that 16-month-old mice born to dams exposed to perinatal TCDD as described above exhibited significantly reduced spine densities. These results indicated that abnormal micromorphology observed in the developing brain may persist until adulthood and may induce abnormal higher brain function later in life.
authors.affiliation: Laboratory of Environmental Health Sciences, Center for Disease Biology and Integrative Medicine, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
authors.forename: Eiki
authors.initials: E
authors.lastname: Kimura
authors.affiliation: Department of Anatomy, Keio University School of Medicine, Tokyo, Japan.
authors.forename: Ken-Ichiro
authors.initials: K
authors.lastname: Kubo
authors.affiliation: Laboratory of Environmental Health Sciences, Center for Disease Biology and Integrative Medicine, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
authors.forename: Chieri
authors.initials: C
authors.lastname: Matsuyoshi
authors.affiliation: Laboratory of Environmental Health Sciences, Center for Disease Biology and Integrative Medicine, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
authors.forename: Seico
authors.initials: S
authors.lastname: Benner
authors.affiliation: Laboratory of Environmental Health Sciences, Center for Disease Biology and Integrative Medicine, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan; Department of Epidemiology and Environmental Health, Juntendo University Faculty of Medicine, Tokyo, Japan.
authors.forename: Mayuko
authors.initials: M
authors.lastname: Hosokawa
authors.affiliation: Laboratory of Environmental Health Sciences, Center for Disease Biology and Integrative Medicine, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
authors.forename: Toshihiro
authors.initials: T
authors.lastname: Endo
authors.affiliation: Laboratory of Environmental Health Sciences, Center for Disease Biology and Integrative Medicine, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
authors.forename: Wenting
authors.initials: W
authors.lastname: Ling
authors.affiliation: Laboratory of Environmental Health Sciences, Center for Disease Biology and Integrative Medicine, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
authors.forename: Masanobu
authors.initials: M
authors.lastname: Kohda
authors.affiliation: Department of Epidemiology and Environmental Health, Juntendo University Faculty of Medicine, Tokyo, Japan.
authors.forename: Kazuhito
authors.initials: K
authors.lastname: Yokoyama
authors.affiliation: Department of Anatomy, Keio University School of Medicine, Tokyo, Japan.
authors.forename: Kazunori
authors.initials: K
authors.lastname: Nakajima
authors.affiliation: Laboratory of Environmental Health Sciences, Center for Disease Biology and Integrative Medicine, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan; Laboratory for Systems Neuroscience and Preventive Medicine, Faculty of Human Sciences, Waseda University, Tokorozawa, Japan.
authors.forename: Masaki
authors.initials: M
authors.lastname: Kakeyama
authors.affiliation: Laboratory of Environmental Health Sciences, Center for Disease Biology and Integrative Medicine, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan; Enviornmental Biology Laboratory, Faculty of Medicine, University of Tsukuba, Tsukuba, Japan. Electronic address: tohyamac-tky@umin.org.
authors.forename: Chiharu
authors.initials: C
authors.lastname: Tohyama
mesh_terms: D000679:Amygdala / Q000187:drug effects / Q000254:growth & development / Q000473:pathology; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000254:growth & development / Q000473:pathology; D003712:Dendrites / Q000187:drug effects* / Q000473:pathology*; D049229:Dendritic Spines / Q000187:drug effects / Q000473:pathology; D004305:Dose-Response Relationship, Drug; D004785:Environmental Pollutants / Q000032:analysis / Q000633:toxicity*; D005260:Female; D006624:Hippocampus / Q000187:drug effects* / Q000254:growth & development* / Q000378:metabolism / Q000473:pathology*; D008297:Male; D018811:Maternal Exposure; D051379:Mice; D008810:Mice, Inbred C57BL; D000072317:Polychlorinated Dibenzodioxins / Q000032:analysis / Q000633:toxicity*; D017966:Pyramidal Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D018336:Receptors, Aryl Hydrocarbon / Q000378:metabolism*
chemical_list: D004785:Environmental Pollutants; D000072317:Polychlorinated Dibenzodioxins; D018336:Receptors, Aryl Hydrocarbon
keywords: Aryl hydrocarbon receptor; Dendrite; Developmental neurotoxicity; Dioxin; Hippocampus; Spine