title: Transient aberration of neuronal development in the hippocampal dentate gyrus after developmental exposure to brominated flame retardants in rats.
abstract: We immunohistochemically investigated the impact and reversibility of three brominated flame retardants (BFRs) known to be weak thyroid hormone disruptors on neuronal development in the hippocampal formation and apoptosis in the dentate subgranular zone. Pregnant Sprague-Dawley rats were exposed to 10, 100, or 1,000 ppm decabromodiphenyl ether (DBDE); 100, 1,000 or 10,000 ppm tetrabromobisphenol A (TBBPA) or 1,2,5,6,9,10-hexabromocyclododecane (HBCD) in the diet from gestational day 10 through to day 20 after delivery (weaning). On postnatal day (PND) 20, interneurons in the dentate hilus-expressing reelin increased with all chemicals, suggestive of aberration of neuronal migration. However, this increase had disappeared by PND 77. NeuN-positive mature neurons increased in the hilus on PND 77 with all chemicals. In the subgranular zone on PND 20, an increase in apoptotic bodies suggestive of impaired neurogenesis was observed after exposure to TBBPA or HBCD. The effects on neuronal development were detected at doses of ≥100 ppm DBDE; ≥1,000 ppm TBBPA; and at least at 10,000 ppm HBCD. On PND 20, the highest dose of DBDE and HBCD revealed mild fluctuations in the serum concentrations of thyroid-related hormones suggestive of weak developmental hypothyroidism, while TBBPA did not. Thus, DBDE and TBBPA may exert direct effect on neuronal development in the brain, but hypothyroidism may be operated for DBDE and HBCD at high doses. An excess of mature neurons in the hilus at later stages may be the signature of the developmental effects of BFRs. However, the effect itself was reversible.
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: Yukie
authors.initials: Y
authors.lastname: Saegusa
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Fujimoto
authors.forename: Gye-Hyeong
authors.initials: GH
authors.lastname: Woo
authors.forename: Takumi
authors.initials: T
authors.lastname: Ohishi
authors.forename: Liyun
authors.initials: L
authors.lastname: Wang
authors.forename: Kunitoshi
authors.initials: K
authors.lastname: Mitsumori
authors.forename: Akiyoshi
authors.initials: A
authors.lastname: Nishikawa
authors.forename: Makoto
authors.initials: M
authors.lastname: Shibutani
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D015415:Biomarkers / Q000378:metabolism; D018891:Dentate Gyrus / Q000187:drug effects* / Q000254:growth & development / Q000378:metabolism / Q000473:pathology; D004305:Dose-Response Relationship, Drug; D005260:Female; D005411:Flame Retardants / Q000008:administration & dosage / Q000633:toxicity*; D055768:Halogenated Diphenyl Ethers / Q000008:administration & dosage / Q000633:toxicity; D006842:Hydrocarbons, Brominated / Q000008:administration & dosage / Q000633:toxicity*; D007395:Interneurons / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D007774:Lactation; D008297:Male; D018811:Maternal Exposure / Q000009:adverse effects; D009419:Nerve Tissue Proteins / Q000378:metabolism; D055495:Neurogenesis / Q000187:drug effects*; D011075:Polybrominated Biphenyls / Q000008:administration & dosage / Q000633:toxicity; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D000091042:Reelin Protein
chemical_list: D015415:Biomarkers; D005411:Flame Retardants; D055768:Halogenated Diphenyl Ethers; D006842:Hydrocarbons, Brominated; D009419:Nerve Tissue Proteins; D011075:Polybrominated Biphenyls; D000091042:Reelin Protein; C000717129:Reln protein, rat; C089796:hexabromocyclododecane; C020806:tetrabromobisphenol A; C010902:decabromobiphenyl ether