IUF- Leibniz Research Institute for Environmental Medicine, Auf'm Hennekamp 50, 40225, Duesseldorf, Germany.
Department of Molecular Biosciences, School of Veterinary Medicine, University of California, Davis, California 95616, United States.
Sci Rep. 2017 Mar 20;7:44861. doi: 10.1038/srep44861.
Polybrominated diphenyl ethers (PBDEs) are bioaccumulating flame retardants causing developmental neurotoxicity (DNT) in humans and rodents. Their DNT effects are suspected to involve thyroid hormone (TH) signaling disruption. Here, we tested the hypothesis whether disturbance of neural progenitor cell (NPC) differentiation into the oligodendrocyte lineage (O4 cells) by BDE-99 involves disruption of TH action in human and mouse (h,m)NPCs. Therefore, we quantified differentiation of NPCs into O4 cells and measured their maturation via expression of myelin-associated genes (hMBP, mMog) in presence and absence of TH and/or BDE-99. T3 promoted O4 cell differentiation in mouse, but not hNPCs, and induced hMBP/mMog gene expression in both species. BDE-99 reduced generation of human and mouse O4 cells, but there is no indication for BDE-99 interfering with cellular TH signaling during O4 cell formation. BDE-99 reduced hMBP expression due to oligodendrocyte reduction, but concentrations that did not affect the number of mouse O4 cells inhibited TH-induced mMog transcription by a yet unknown mechanism. In addition, ascorbic acid antagonized only the BDE-99-dependent loss of human, not mouse, O4 cells by a mechanism probably independent of reactive oxygen species. These data point to species-specific modes of action of BDE-99 on h/mNPC development into the oligodendrocyte lineage.
多溴联苯醚 (PBDEs) 是具有生物累积性的阻燃剂，会对人类和啮齿动物造成发育神经毒性 (DNT)。它们的 DNT 效应据推测涉及甲状腺激素 (TH) 信号中断。在这里，我们测试了以下假设：BDE-99 是否通过干扰神经祖细胞 (NPC) 向少突胶质细胞谱系 (O4 细胞) 的分化，从而破坏人源和鼠源 (h,m)NPC 中的 TH 作用。因此，我们通过检测髓鞘相关基因 (hMBP、mMog) 的表达，来定量 NPC 分化为 O4 细胞的情况，并测量其成熟度，检测时存在或不存在 TH 和/或 BDE-99。T3 促进了小鼠 NPC 向 O4 细胞的分化，但不促进人源 NPC 的分化，并且在两种物种中均诱导 hMBP/mMog 基因的表达。BDE-99 减少了人源和鼠源 O4 细胞的生成，但没有迹象表明 BDE-99 在 O4 细胞形成过程中干扰细胞内的 TH 信号。BDE-99 降低了 hMBP 的表达，原因是少突胶质细胞减少，但不会影响小鼠 O4 细胞数量的浓度，通过未知的机制抑制了 TH 诱导的 mMog 转录。此外，抗坏血酸仅拮抗 BDE-99 依赖性的人源而非鼠源 O4 细胞的损失，其机制可能独立于活性氧。这些数据表明 BDE-99 对 h/mNPC 向少突胶质细胞谱系发育的作用具有种属特异性。
