脑源性神经营养因子（BDNF）可改善六溴环十二烷（HBCD）对甲状腺激素诱导颗粒细胞突起生长的抑制作用。

Brain-derived neurotrophic factor (BDNF) ameliorates the suppression of thyroid hormone-induced granule cell neurite extension by hexabromocyclododecane (HBCD).

机构信息

Department of Integrative Physiology, Gunma University Graduate School of Medicine, 3-39-22 Showa-machi, Maebashi, Gunma 371-8511, Japan.

出版信息

Neurosci Lett. 2011 Apr 8;493(1-2):1-7. doi: 10.1016/j.neulet.2011.01.062. Epub 2011 Jan 31.

DOI:10.1016/j.neulet.2011.01.062

PMID:21281695

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.

摘要

甲状腺激素（TH）在中枢神经系统的生长和分化中起着至关重要的作用。围产期 TH 缺乏会导致大脑发育异常，称为人类呆小症。我们最近报道，一种环境化学物质 1,2,5,6,9,10-α-六溴环十二烷（HBCD）抑制了 TH 受体（TR）介导的转录。为了研究 HBCD 对小脑颗粒细胞的影响，我们使用纯化的大鼠小脑颗粒细胞再聚集培养。低剂量 HBCD（10（-10）M）显著抑制了 TH 诱导的颗粒细胞聚集的神经突延伸。为了进一步阐明这种抑制的机制，我们在培养物中添加了脑源性神经营养因子（BDNF），因为 BDNF 在促进颗粒细胞发育中起着关键作用，并受 TH 调节。在 T3 存在的情况下，BDNF 完全挽救了 HBCD 诱导的颗粒细胞神经突延伸的抑制。这些结果表明，HBCD 可能会破坏 TH 介导的大脑发育，至少部分原因是破坏了 T3 刺激的 BDNF 增加，而 BDNF 可能具有改善颗粒细胞中 HBCD 作用的能力。