Immunohistochemical analysis of 2,3,7,8-tetrachlorodibenzo-p-dioxin (Tcdd) toxicity on the developmental dentate gyrus and hippocampal fimbria in fetal mice

Yoshihiro Kobayashi, Tetsushi Hirano, Takuya Omotehara, Rie Hashimoto, Yuria Umemura, Hideto Yuasa, Natsumi Masuda, Naoto Kubota, Kiichi Minami, Shogo Yanai, Mitsuko Ishihara-Sugano, Youhei Mantani, Toshifumi Yokoyama, Hiroshi Kitagawa, Nobuhiko Hoshi

Research output: Contribution to journalArticlepeer-review

8 Citations (Scopus)


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.

Original languageEnglish
Pages (from-to)1355-1361
Number of pages7
JournalJournal of Veterinary Medical Science
Issue number11
Publication statusPublished - Dec 1 2015
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • veterinary(all)


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