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Brominated and organophosphate flame retardants target different neurodevelopmental stages, characterized with embryonic neural stem cells and neuronotypic PC12 cells.

Publication ,  Journal Article
Slotkin, TA; Skavicus, S; Stapleton, HM; Seidler, FJ
Published in: Toxicology
September 2017

In addition to their activity as endocrine disruptors, brominated and organophosphate flame retardants are suspected to be developmental neurotoxicants, although identifying their specific mechanisms for that activity has been elusive. In the current study, we evaluated the effects of several flame retardants on neurodifferentiation using two in vitro models that assess distinct "decision nodes" in neural cell development: embryonic rat neural stem cells (NSCs), which evaluate the origination of neurons and glia from precursors, and rat neuronotypic PC12 cells, which characterize a later stage where cells committed to a neuronal phenotype undergo neurite outgrowth and neurotransmitter specification. In NSCs, both brominated and organophosphate flame retardants diverted the phenotype in favor of glia and away from formation of neurons, leading to an increased glia/neuron ratio, a common hallmark of the in vivo effects of neurotoxicants. For this early decision node, the brominated flame retardants were far more potent than the organophosphates. In PC12 cells, the brominated flame retardants were far less effective, whereas tris (1,3-dichloro-2-propyl) phosphate, an organophosphate, was more effective. Thus, the two classes of flame retardants differentially impact the two distinct vulnerable periods of neurodifferentiation. Furthermore, the effects on neurodifferentiation were separable from outright cytotoxicity, an important requirement in establishing a specific effect of these agents on neural cell development. These results reinforce the likelihood that flame retardants act as developmental neurotoxicants via direct effects on neural cell differentiation, over and above other activities that can impact nervous system development, such as endocrine disruption.

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Published In

Toxicology

DOI

EISSN

1879-3185

ISSN

0300-483X

Publication Date

September 2017

Volume

390

Start / End Page

32 / 42

Related Subject Headings

  • Toxicology
  • Risk Assessment
  • Rats
  • Polybrominated Biphenyls
  • Phenotype
  • PC12 Cells
  • Organophosphorus Compounds
  • Neurotoxicity Syndromes
  • Neuroglia
  • Neurogenesis
 

Citation

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Slotkin, T. A., Skavicus, S., Stapleton, H. M., & Seidler, F. J. (2017). Brominated and organophosphate flame retardants target different neurodevelopmental stages, characterized with embryonic neural stem cells and neuronotypic PC12 cells. Toxicology, 390, 32–42. https://doi.org/10.1016/j.tox.2017.08.009
Slotkin, Theodore A., Samantha Skavicus, Heather M. Stapleton, and Frederic J. Seidler. “Brominated and organophosphate flame retardants target different neurodevelopmental stages, characterized with embryonic neural stem cells and neuronotypic PC12 cells.Toxicology 390 (September 2017): 32–42. https://doi.org/10.1016/j.tox.2017.08.009.
Slotkin, Theodore A., et al. “Brominated and organophosphate flame retardants target different neurodevelopmental stages, characterized with embryonic neural stem cells and neuronotypic PC12 cells.Toxicology, vol. 390, Sept. 2017, pp. 32–42. Epmc, doi:10.1016/j.tox.2017.08.009.
Journal cover image

Published In

Toxicology

DOI

EISSN

1879-3185

ISSN

0300-483X

Publication Date

September 2017

Volume

390

Start / End Page

32 / 42

Related Subject Headings

  • Toxicology
  • Risk Assessment
  • Rats
  • Polybrominated Biphenyls
  • Phenotype
  • PC12 Cells
  • Organophosphorus Compounds
  • Neurotoxicity Syndromes
  • Neuroglia
  • Neurogenesis