title: Glycidol induces axonopathy and aberrations of hippocampal neurogenesis affecting late-stage differentiation by exposure to rats in a framework of 28-day toxicity study.
abstract: Developmental exposure to glycidol induces aberrations of late-stage neurogenesis in the hippocampal dentate gyrus of rat offspring, whereas maternal animals develop axonopathy. To investigate the possibility whether similar effects on adult neurogenesis could be induced by exposure in a framework of 28-day toxicity study, glycidol was orally administered to 5-week-old male Sprague-Dawley rats by gavage at 0, 30 or 200 mg/kg for 28 days. At 200 mg/kg, animals revealed progressively worsening gait abnormalities as well as histopathological and immunohistochemical changes suggestive of axonal injury as evidenced by generation of neurofilament-L(+) spheroids in the cerebellar granule layer and dorsal funiculus of the medulla oblongata, central chromatolysis in the trigeminal nerve ganglion cells and axonal degeneration in the sciatic nerves. At the same dose, animals revealed aberrations in neurogenesis at late-stage differentiation as evidenced by decreases of both doublecortin(+) and dihydropyrimidinase-like 3(+) cells in the subgranular zone (SGZ) and increased reelin(+) or calbindin-2(+) γ-aminobutyric acid-ergic interneurons and neuron-specific nuclear protein(+) mature neurons in the dentate hilus. These effects were essentially similar to that observed in offspring after maternal exposure to glycidol. These results suggest that glycidol causes aberrations in adult neurogenesis in the SGZ at the late stage involving the process of neurite extension similar to the developmental exposure study in a standard 28-day toxicity study.
authors.affiliation: Laboratory of Veterinary Pathology, Tokyo University of Agriculture and Technology, 3-5-8 Saiwai-cho, Fuchu-shi, Tokyo 183-8509, Japan.
authors.forename: Hirotoshi
authors.initials: H
authors.lastname: Akane
authors.affiliation: Laboratory of Veterinary Pathology, Tokyo University of Agriculture and Technology, 3-5-8 Saiwai-cho, Fuchu-shi, Tokyo 183-8509, Japan; Pathogenetic Veterinary Science, United Graduate School of Veterinary Sciences, Gifu University, 1-1 Yanagido, Gifu-shi, Gifu 501-1193, Japan.
authors.forename: Ayako
authors.initials: A
authors.lastname: Shiraki
authors.affiliation: Chemicals Evaluation and Research Institute, 1-4-25 Koraku, Bunkyo-ku, Tokyo 112-0004, Japan.
authors.forename: Nobuya
authors.initials: N
authors.lastname: Imatanaka
authors.affiliation: Chemicals Evaluation and Research Institute, 1-4-25 Koraku, Bunkyo-ku, Tokyo 112-0004, Japan.
authors.forename: Yumi
authors.initials: Y
authors.lastname: Akahori
authors.affiliation: Laboratory of Veterinary Pathology, Tokyo University of Agriculture and Technology, 3-5-8 Saiwai-cho, Fuchu-shi, Tokyo 183-8509, Japan; Pathogenetic Veterinary Science, United Graduate School of Veterinary Sciences, Gifu University, 1-1 Yanagido, Gifu-shi, Gifu 501-1193, Japan.
authors.forename: Megu
authors.initials: M
authors.lastname: Itahashi
authors.affiliation: Laboratory of Veterinary Pathology, Tokyo University of Agriculture and Technology, 3-5-8 Saiwai-cho, Fuchu-shi, Tokyo 183-8509, Japan; Pathogenetic Veterinary Science, United Graduate School of Veterinary Sciences, Gifu University, 1-1 Yanagido, Gifu-shi, Gifu 501-1193, Japan.
authors.forename: Hajime
authors.initials: H
authors.lastname: Abe
authors.affiliation: Laboratory of Veterinary Pathology, Tokyo University of Agriculture and Technology, 3-5-8 Saiwai-cho, Fuchu-shi, Tokyo 183-8509, Japan. Electronic address: mshibuta@cc.tuat.ac.jp.
authors.forename: Makoto
authors.initials: M
authors.lastname: Shibutani
mesh_terms: D000818:Animals; D034961:Antigens, Nuclear / Q000378:metabolism; D017209:Apoptosis / Q000187:drug effects; D001369:Axons / Q000473:pathology*; D002273:Carcinogens / Q000633:toxicity*; D002452:Cell Count; D002454:Cell Differentiation / Q000187:drug effects*; D018891:Dentate Gyrus / Q000187:drug effects / Q000254:growth & development; D000089662:Doublecortin Protein; D004852:Epoxy Compounds / Q000633:toxicity*; D005260:Female; D020233:Gait Disorders, Neurologic / Q000139:chemically induced / Q000473:pathology; D006624:Hippocampus / Q000166:cytology* / Q000187:drug effects* / Q000254:growth & development; D006728:Hormones / Q000097:blood; D007150:Immunohistochemistry; D007395:Interneurons / Q000187:drug effects / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000378:metabolism; D055495:Neurogenesis / Q000187:drug effects*; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D020005:Propanols / Q000633:toxicity*; D051381:Rats; D017207:Rats, Sprague-Dawley; D060888:Real-Time Polymerase Chain Reaction; D000091042:Reelin Protein; D013234:Stem Cells / Q000187:drug effects; D013963:Thyroid Hormones / Q000097:blood
chemical_list: D034961:Antigens, Nuclear; D002273:Carcinogens; C000714848:Dcx protein, rat; D000089662:Doublecortin Protein; D004852:Epoxy Compounds; D006728:Hormones; D009419:Nerve Tissue Proteins; D020005:Propanols; C546339:Rbfox3 protein, rat; D000091042:Reelin Protein; C000717129:Reln protein, rat; D013963:Thyroid Hormones; C004312:glycidol
keywords: 3,3′-diaminobenzidine; Axonopathy; C(T); Calb1; Calb2; Calbindin-D-28K; Calretinin; DAB; DCX; Dihydropyrimidinase-like 3; Doublecortin; Dpysl3; GABA; GFAP; Gamma-aminobutyric acid; Gapdh; Glial fibrillary acidic protein; Glyceraldehyde 3-phosphate dehydrogenase; Glycidol; Hippocampal dentate gyrus; Hprt; Hypoxanthine phosphoribosyltransferase 1; MMI; Methimazole; NF-L; NeuN; Neurofilament-L; Neurogenesis; Neuron-specific nuclear protein; Neurotoxicity; PBS; PCNA; Paired box 6; Parvalbumin; Pax6; Phosphate-buffered saline; Phosphorylated neurofilament-H; Proliferating cell nuclear antigen; Pvalb; RT-PCR; Reverse-transcription polymerase chain reaction; SGZ; Subgranular zone; T box brain 2; T(3); T(4); TSH; TUNEL; Tbr2; Terminal deoxynucleotidyl transferase dUTP nick end labeling; Threshold cycle; Thyroid-stimulating hormone; Thyroxine; Triiodothyronine; p-NF-H