BDE-99 impairs differentiation of human and mouse NPCs into the oligodendroglial lineage by species-specific modes of action.
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.
IUF- Leibniz Research Institute for Environmental Medicine, Auf'm Hennekamp 50, 40225, Duesseldorf, Germany.
Katharina
K
Dach
IUF- Leibniz Research Institute for Environmental Medicine, Auf'm Hennekamp 50, 40225, Duesseldorf, Germany.
Farina
F
Bendt
IUF- Leibniz Research Institute for Environmental Medicine, Auf'm Hennekamp 50, 40225, Duesseldorf, Germany.
Ulrike
U
Huebenthal
IUF- Leibniz Research Institute for Environmental Medicine, Auf'm Hennekamp 50, 40225, Duesseldorf, Germany.
Susanne
S
Giersiefer
Department of Molecular Biosciences, School of Veterinary Medicine, University of California, Davis, California 95616, United States.
Pamela J
PJ
Lein
IUF- Leibniz Research Institute for Environmental Medicine, Auf'm Hennekamp 50, 40225, Duesseldorf, Germany.
Heike
H
Heuer
IUF- Leibniz Research Institute for Environmental Medicine, Auf'm Hennekamp 50, 40225, Duesseldorf, Germany.
Ellen
E
Fritsche
D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects*; D002460:Cell Line; D019070:Cell Lineage; D055768:Halogenated Diphenyl Ethers / Q000494:pharmacology*; D006801:Humans; D051379:Mice; D008869:Microtubule-Associated Proteins / Q000235:genetics / Q000378:metabolism; D058953:Neural Stem Cells / Q000166:cytology* / Q000187:drug effects* / Q000378:metabolism; D009836:Oligodendroglia / Q000166:cytology* / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D013045:Species Specificity; D014446:Tyrosine 3-Monooxygenase
C477694:2,2',4,4',5-brominated diphenyl ether; C587430:CKAP5 protein, mouse; D055768:Halogenated Diphenyl Ethers; D008869:Microtubule-Associated Proteins; D017382:Reactive Oxygen Species; D014446:Tyrosine 3-Monooxygenase