PMID- 26526904 OWN - NLM STAT- MEDLINE DCOM- 20161012 LR - 20170103 IS - 1872-9738 (Electronic) IS - 0892-0362 (Linking) VI - 52 IP - Pt A DP - 2015 Nov-Dec TI - Developmental origin of abnormal dendritic growth in the mouse brain induced by in utero disruption of aryl hydrocarbon receptor signaling. PG - 42-50 LID - S0892-0362(15)30039-8 [pii] LID - 10.1016/j.ntt.2015.10.005 [doi] AB - 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 mug/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. CI - Copyright (c) 2015 The Authors. Published by Elsevier Inc. All rights reserved. FAU - Kimura, Eiki AU - Kimura E AD - Laboratory of Environmental Health Sciences, Center for Disease Biology and Integrative Medicine, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan. FAU - Kubo, Ken-Ichiro AU - Kubo K AD - Department of Anatomy, Keio University School of Medicine, Tokyo, Japan. FAU - Matsuyoshi, Chieri AU - Matsuyoshi C AD - Laboratory of Environmental Health Sciences, Center for Disease Biology and Integrative Medicine, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan. FAU - Benner, Seico AU - Benner S AD - Laboratory of Environmental Health Sciences, Center for Disease Biology and Integrative Medicine, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan. FAU - Hosokawa, Mayuko AU - Hosokawa M AD - 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. FAU - Endo, Toshihiro AU - Endo T AD - Laboratory of Environmental Health Sciences, Center for Disease Biology and Integrative Medicine, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan. FAU - Ling, Wenting AU - Ling W AD - Laboratory of Environmental Health Sciences, Center for Disease Biology and Integrative Medicine, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan. FAU - Kohda, Masanobu AU - Kohda M AD - Laboratory of Environmental Health Sciences, Center for Disease Biology and Integrative Medicine, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan. FAU - Yokoyama, Kazuhito AU - Yokoyama K AD - Department of Epidemiology and Environmental Health, Juntendo University Faculty of Medicine, Tokyo, Japan. FAU - Nakajima, Kazunori AU - Nakajima K AD - Department of Anatomy, Keio University School of Medicine, Tokyo, Japan. FAU - Kakeyama, Masaki AU - Kakeyama M AD - 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. FAU - Tohyama, Chiharu AU - Tohyama C AD - 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. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20151023 PL - United States TA - Neurotoxicol Teratol JT - Neurotoxicology and teratology JID - 8709538 RN - 0 (Environmental Pollutants) RN - 0 (Polychlorinated Dibenzodioxins) RN - 0 (Receptors, Aryl Hydrocarbon) SB - IM MH - Amygdala/drug effects/growth & development/pathology MH - Animals MH - Brain/drug effects/growth & development/pathology MH - Dendrites/*drug effects/*pathology MH - Dendritic Spines/drug effects/pathology MH - Dose-Response Relationship, Drug MH - Environmental Pollutants/analysis/*toxicity MH - Female MH - Hippocampus/*drug effects/*growth & development/metabolism/*pathology MH - Male MH - Maternal Exposure MH - Mice MH - Mice, Inbred C57BL MH - Polychlorinated Dibenzodioxins/analysis/*toxicity MH - Pyramidal Cells/drug effects/metabolism/pathology MH - Receptors, Aryl Hydrocarbon/*metabolism OTO - NOTNLM OT - Aryl hydrocarbon receptor OT - Dendrite OT - Developmental neurotoxicity OT - Dioxin OT - Hippocampus OT - Spine EDAT- 2015/11/04 06:00 MHDA- 2016/10/13 06:00 CRDT- 2015/11/04 06:00 PHST- 2015/02/08 00:00 [received] PHST- 2015/09/26 00:00 [revised] PHST- 2015/10/21 00:00 [accepted] PHST- 2015/11/04 06:00 [entrez] PHST- 2015/11/04 06:00 [pubmed] PHST- 2016/10/13 06:00 [medline] AID - S0892-0362(15)30039-8 [pii] AID - 10.1016/j.ntt.2015.10.005 [doi] PST - ppublish SO - Neurotoxicol Teratol. 2015 Nov-Dec;52(Pt A):42-50. doi: 10.1016/j.ntt.2015.10.005. Epub 2015 Oct 23.