title: Brain-derived neurotrophic factor (BDNF) ameliorates the suppression of thyroid hormone-induced granule cell neurite extension by hexabromocyclododecane (HBCD).
abstract: Thyroid hormone (TH) plays an essential role in growth and differentiation of the central nervous system. Deficiency of TH during perinatal period results in abnormal brain development known as cretinism in human. We recently reported that an environmental chemical 1,2,5,6,9,10-α-hexabromocyclododecane (HBCD) suppressed TH receptor (TR)-mediated transcription. To examine the effect of HBCD on cerebellar granule cells, we used purified rat cerebellar granule cells in reaggregate culture. Low dose HBCD (10(-10)M) significantly suppressed TH-induced neurite extension of granule cell aggregate. To clarify further the mechanisms of such suppression, we added brain-derived neurotrophic factor (BDNF) into culture medium, since BDNF plays a critical role in promoting granule cell development and is regulated by TH. BDNF completely rescued HBCD-induced suppression of granule cell neurite extension in the presence of T3. These results indicate that HBCD may disrupt TH-mediated brain development at least in part due to a disruption of the T3 stimulated increase in BDNF and BDNF may possess ability to ameliorate the effect of HBCD in granule cells.
authors.affiliation: Department of Integrative Physiology, Gunma University Graduate School of Medicine, 3-39-22 Showa-machi, Maebashi, Gunma 371-8511, Japan.
authors.forename: Kingsley
authors.initials: K
authors.lastname: Ibhazehiebo
authors.forename: Toshiharu
authors.initials: T
authors.lastname: Iwasaki
authors.forename: Ming
authors.initials: M
authors.lastname: Xu
authors.forename: Noriaki
authors.initials: N
authors.lastname: Shimokawa
authors.forename: Noriyuki
authors.initials: N
authors.lastname: Koibuchi
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D013956:Antithyroid Agents / Q000633:toxicity; D019208:Brain-Derived Neurotrophic Factor / Q000502:physiology*; D002454:Cell Differentiation / Q000187:drug effects* / Q000502:physiology; D002478:Cells, Cultured; D002531:Cerebellum / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D006842:Hydrocarbons, Brominated / Q000037:antagonists & inhibitors* / Q000633:toxicity; D016501:Neurites / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D018696:Neuroprotective Agents / Q000494:pharmacology*; D009498:Neurotoxins / Q000037:antagonists & inhibitors / Q000633:toxicity; D051381:Rats; D017208:Rats, Wistar; D013963:Thyroid Hormones / Q000494:pharmacology* / Q000502:physiology
chemical_list: D013956:Antithyroid Agents; D019208:Brain-Derived Neurotrophic Factor; D006842:Hydrocarbons, Brominated; D018696:Neuroprotective Agents; D009498:Neurotoxins; D013963:Thyroid Hormones; C089796:hexabromocyclododecane