Immunohistochemical analysis of2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) toxicity on the developmentaldentate gyrus and hippocampal fimbria in fetal mice

Journal of Veterinary Medical Science

Kiichi MINAMI²  Mitsuko ISHIHARA-SUGANO³  Shogo YANAI²  Tetsushi HIRANO²  Takuya OMOTEHARA²  Hideto YUASA¹  Yoshihiro KOBAYASHI²  Rie HASHIMOTO²  Naoto KUBOTA²  Nobuhiko HOSHI²  Youhei MANTANI¹  Yuria UMEMURA²  Hiroshi KITAGAWA¹  Toshifumi YOKOYAMA²  Natsumi MASUDA¹ 

[1] Laboratory of Histophysiology, Department of Animal Science, Graduate School of Agricultural Science, Kobe University, Kobe, Hyogo 657�?8501, Japan;Laboratory of Molecular Morphology, Department of Animal Science, Graduate School of Agricultural Science, Kobe University, Kobe, Hyogo 657�?8501, Japan;Frontier Research Laboratory, Corporate Research and Development Center, Toshiba Corporation, Saiwai, Kawasaki, Kanagawa 212�?8582, Japan

关键词: aryl hydrocarbon receptor (AhR);    dentate gyrus;    Glial Fibrillary Acidic Protein (GFAP);    hippocampus;    2;    3;    7;    8-tetrachlorodibenzo-p-dioxin (TCDD);   

DOI  :  10.1292/jvms.15-0238

学科分类：兽医学

来源: Japanese Society of Veterinary Science

【 摘 要 】

References(50)Dioxins are widespread persistent environmental contaminants with adverseimpacts on humans and experimental animals. Behavioral and cognitive functions areimpaired by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) exposure. TCDDexerts its toxicity via the aryl hydrocarbon receptor (AhR), a ligand-activatedtranscription factor. The hippocampus, which plays important roles in episodic memory andspatial function, is considered vulnerable to TCDD-induced neurotoxicity, because itcontains the AhR. We herein investigated the effects of TCDD toxicity on hippocampaldevelopment in embryonic mice. TCDD was administered to dams at 8.5 days postcoitum with asingle 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 atembryonic day 18.5. Immunohistochemical analysis demonstrated that the Glial FibrillaryAcidic Protein (GFAP) immunoreactivities in the dentate gyrus (DG) were reduced in theT5000 group. Granular GFAP immunoreactivity was observed in the hippocampal fimbria, andthe number of immunoreactive fimbria was significantly decreased in the T5000 group. Thenumber of Proliferating Cell Nuclear Antigen (PCNA)-positive cells was decreased in allTCDD-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 stemcells (NSCs), neural precursor cells (NPCs) and granular cells in the DG and disrupts theNSC maintenance and timing of differentiation in the hippocampal fimbria, which in turninterrupt neuronal development in future generations of mice.

【 授权许可】

Unknown