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1,2,5,6,9,10-αHexabromocyclododecane (HBCD) Impairs Thyroid Hormone-Induced Dendrite Arborization of Purkinje Cells and Suppresses Thyroid Hormone Receptor-Mediated Transcription

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Abstract

1,2,5,6,9,10-αHexabromocyclododecane (HBCD) is a nonaromatic, brominated cyclic alkane used as an additive flame retardant. It bioaccumulates, persists in the environment, and has been detected in humans and wildlife. Its developmental neurotoxicity is of great concern. We investigated the effect of HBCD on thyroid hormone (TH) receptor (TR)-mediated transcription using transient transfection-based reporter gene assays and found that a low-dose (10−10 M) HBCD suppressed TR-mediated transcription. We further examined the effect of HBCD on interaction of TR with TH response element (TRE) and found a partial dissociation of TR from TRE. HBCD did not dissociate steroid receptor coactivator-1 from TR in the presence of TH; neither did it recruit corepressors (N-CoR and SMRT) to TR in the absence of TH. Furthermore, low-dose HBCD (10−10 M) significantly suppressed TH-induced dendrite arborization of Purkinje cells in primary cerebellar culture derived from newborn rat. These results show that low-dose HBCD can potentially disrupt TR-mediated transactivation and impairs Purkinje cell dendritogenesis, suggesting that HBCD can interfere with TH action in target organs, including the developing brain.

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Acknowledgement

We thank Drs. W. Miyazaki, J. Kimura-Kuroda, T. Aoki, K. Takata, K. Hanamura, and T. Shirao for helpful assistance, and Dr. A. Takeshita for kindly providing plasmids. This project was supported in part by Grants-in-Aid for Scientific Research from the Ministry of Education, Culture, Sports, Science and Technology of Japan (MEXT) (17510039, T.I, 17390060, N.K), and a grant from Ministry of the Environment of Japan (to N.K, T.I, and N.S).

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All authors declare no conflict of interest.

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Authors and Affiliations

  1. Department of Integrative Physiology, Division of Biological Regulations, Gunma University Graduate School of Medicine, Maebashi, Gunma, 371-8511, Japan

    Kingsley Ibhazehiebo, Toshiharu Iwasaki, Noriaki Shimokawa & Noriyuki Koibuchi

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  1. Kingsley Ibhazehiebo
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  2. Toshiharu Iwasaki
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  3. Noriaki Shimokawa
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  4. Noriyuki Koibuchi
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Correspondence to Toshiharu Iwasaki.

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Ibhazehiebo, K., Iwasaki, T., Shimokawa, N. et al. 1,2,5,6,9,10-αHexabromocyclododecane (HBCD) Impairs Thyroid Hormone-Induced Dendrite Arborization of Purkinje Cells and Suppresses Thyroid Hormone Receptor-Mediated Transcription. Cerebellum 10, 22–31 (2011). https://doi.org/10.1007/s12311-010-0218-1

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