title: In utero and lactational dioxin exposure induces Sema3b and Sema3g gene expression in the developing mouse brain.
abstract: In the developing mammalian brain, neural network formation is regulated by complex signaling cascades. In utero and lactational dioxin exposure is known to induce higher brain function abnormalities and dendritic growth disruption in rodents. However, it is unclear whether perinatal dioxin exposure affects the expression of genes involved in neural network formation. Therefore, we investigated changes in gene expression in the brain regions of developing mice born to dams administered 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD; dose: 0, 0.6, or 3.0 μg/kg) on gestational day 12.5. Quantitative RT-PCR showed that TCDD exposure induced Ahrr expression in the cerebral cortex, hippocampus, and olfactory bulb of 3-day-old mice. Gene microarray analysis indicated that the mRNA expression levels of Sema3b and Sema3g, which encode proteins that are known to control axonal projections, were elevated in the olfactory bulb of TCDD-exposed mice, and the induction of these genes was observed during a 2-week postnatal period. Increased Sema3g expression was also observed in the brain but not in the kidney, liver, lung, and spleen of TCDD-exposed neonatal mice. These results indicate that the Sema3b and Sema3g genes are sensitive to brain-specific induction by dioxin exposure, which may disrupt neural network formation in the mammalian nervous system, thereby leading to abnormal higher brain function in adulthood.
authors.affiliation: Laboratory of Environmental Health Sciences, Center for Disease Biology and Integrative Medicine, Graduate School of Medicine, The University of Tokyo, Japan; Environmental Biology Laboratory, Faculty of Medicine, University of Tsukuba, Tsukuba, Japan.
authors.forename: Eiki
authors.initials: E
authors.lastname: Kimura
authors.affiliation: Laboratory of Environmental Health Sciences, Center for Disease Biology and Integrative Medicine, Graduate School of Medicine, The University of 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, Japan.
authors.forename: Wataru
authors.initials: W
authors.lastname: Yoshioka
authors.affiliation: Laboratory of Environmental Health Sciences, Center for Disease Biology and Integrative Medicine, Graduate School of Medicine, The University of Tokyo, Japan.
authors.forename: Yunjie
authors.initials: Y
authors.lastname: Ding
authors.affiliation: Laboratory of Environmental Health Sciences, Center for Disease Biology and Integrative Medicine, Graduate School of Medicine, The University of Tokyo, Japan.
authors.forename: Waka
authors.initials: W
authors.lastname: Ujita
authors.affiliation: Laboratory of Environmental Health Sciences, Center for Disease Biology and Integrative Medicine, Graduate School of Medicine, The University of 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, Japan; Environmental 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: D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics; D001921:Brain / Q000002:abnormalities / Q000187:drug effects* / Q000254:growth & development* / Q000378:metabolism; D004785:Environmental Pollutants / Q000008:administration & dosage / Q000633:toxicity*; D005260:Female; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects; D007774:Lactation / Q000187:drug effects; D018811:Maternal Exposure / Q000009:adverse effects*; D051379:Mice; D008810:Mice, Inbred C57BL; D009830:Olfactory Bulb / Q000002:abnormalities / Q000187:drug effects / Q000254:growth & development / Q000378:metabolism; D000072317:Polychlorinated Dibenzodioxins / Q000008:administration & dosage / Q000633:toxicity*; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000139:chemically induced / Q000235:genetics; D012097:Repressor Proteins / Q000235:genetics; D039961:Semaphorins / Q000235:genetics*
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D004785:Environmental Pollutants; D000072317:Polychlorinated Dibenzodioxins; D012097:Repressor Proteins; D039961:Semaphorins; C117300:Ahrr protein, mouse; C526269:Sema3b protein, mouse; C505763:semaphorin 3G, mouse
keywords: Brain development; Developmental neurotoxicity; Dioxin; Olfactory bulb; Semaphorin