title: Immunohistochemical analysis of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) toxicity on the developmental dentate gyrus and hippocampal fimbria in fetal mice.
abstract: Dioxins are widespread persistent environmental contaminants with adverse impacts on humans and experimental animals. Behavioral and cognitive functions are impaired by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) exposure. TCDD exerts its toxicity via the aryl hydrocarbon receptor (AhR), a ligand-activated transcription factor. The hippocampus, which plays important roles in episodic memory and spatial function, is considered vulnerable to TCDD-induced neurotoxicity, because it contains the AhR. We herein investigated the effects of TCDD toxicity on hippocampal development in embryonic mice. TCDD was administered to dams at 8.5 days postcoitum with a single dose of 20, 200, 2,000 and 5,000 ng/kg body weight (groups T20, T200, T2000 and T5000, respectively), and the brains were dissected from their pups at embryonic day 18.5. Immunohistochemical analysis demonstrated that the Glial Fibrillary Acidic Protein (GFAP) immunoreactivities in the dentate gyrus (DG) were reduced in the T5000 group. Granular GFAP immunoreactivity was observed in the hippocampal fimbria, and the number of immunoreactive fimbria was significantly decreased in the T5000 group. The number of Proliferating Cell Nuclear Antigen (PCNA)-positive cells was decreased in all TCDD-exposed groups and significantly reduced in the T20, T200 and T5000 groups. Together, these results demonstrate that maternal TCDD exposure has adverse impacts on neural stem cells (NSCs), neural precursor cells (NPCs) and granular cells in the DG and disrupts the NSC maintenance and timing of differentiation in the hippocampal fimbria, which in turn interrupt neuronal development in future generations of mice.
authors.affiliation: Laboratory of Molecular Morphology, Department of Animal Science, Graduate School of Agricultural Science, Kobe University, Kobe, Hyogo 657-8501, Japan.
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Kobayashi
authors.forename: Tetsushi
authors.initials: T
authors.lastname: Hirano
authors.forename: Takuya
authors.initials: T
authors.lastname: Omotehara
authors.forename: Rie
authors.initials: R
authors.lastname: Hashimoto
authors.forename: Yuria
authors.initials: Y
authors.lastname: Umemura
authors.forename: Hideto
authors.initials: H
authors.lastname: Yuasa
authors.forename: Natsumi
authors.initials: N
authors.lastname: Masuda
authors.forename: Naoto
authors.initials: N
authors.lastname: Kubota
authors.forename: Kiichi
authors.initials: K
authors.lastname: Minami
authors.forename: Shogo
authors.initials: S
authors.lastname: Yanai
authors.forename: Mitsuko
authors.initials: M
authors.lastname: Ishihara-Sugano
authors.forename: Youhei
authors.initials: Y
authors.lastname: Mantani
authors.forename: Toshifumi
authors.initials: T
authors.lastname: Yokoyama
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kitagawa
authors.forename: Nobuhiko
authors.initials: N
authors.lastname: Hoshi
mesh_terms: D000818:Animals; D001921:Brain / Q000187:drug effects; D018891:Dentate Gyrus / Q000187:drug effects / Q000196:embryology*; D004305:Dose-Response Relationship, Drug; D020567:Fetal Weight / Q000187:drug effects; D006624:Hippocampus / Q000187:drug effects / Q000196:embryology*; D007150:Immunohistochemistry; D051379:Mice; D009929:Organ Size / Q000187:drug effects; D000072317:Polychlorinated Dibenzodioxins / Q000008:administration & dosage / Q000633:toxicity*
chemical_list: D000072317:Polychlorinated Dibenzodioxins