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Diverse neurotoxicants target the differentiation of embryonic neural stem cells into neuronal and glial phenotypes.

Publication ,  Journal Article
Slotkin, TA; Skavicus, S; Card, J; Levin, ED; Seidler, FJ
Published in: Toxicology
November 30, 2016

The large number of compounds that needs to be tested for developmental neurotoxicity drives the need to establish in vitro models to evaluate specific neurotoxic endpoints. We used neural stem cells derived from rat neuroepithelium on embryonic day 14 to evaluate the impact of diverse toxicants on their ability to differentiate into glia and neurons: a glucocorticoid (dexamethasone), organophosphate insecticides (chlorpyrifos, diazinon, parathion), insecticides targeting the GABAA receptor (dieldrin, fipronil), heavy metals (Ni2+, Ag+), nicotine and tobacco smoke extract. We found three broad groupings of effects. One diverse set of compounds, dexamethasone, the organophosphate pesticides, Ni2+ and nicotine, suppressed expression of the glial phenotype while having little or no effect on the neuronal phenotype. The second pattern was restricted to the pesticides acting on GABAA receptors. These compounds promoted the glial phenotype and suppressed the neuronal phenotype. Notably, the actions of compounds eliciting either of these differentiation patterns were clearly unrelated to deficits in cell numbers: dexamethasone, dieldrin and fipronil all reduced cell numbers, whereas organophosphates and Ni2+ had no effect. The third pattern, shared by Ag+ and tobacco smoke extract, clearly delineated cytotoxicity, characterized by major cell loss with suppression of differentiation into both glial and neuronal phenotypes; but here again, there was some selectivity in that glia were suppressed more than neurons. Our results, from this survey with diverse compounds, point to convergence of neurotoxicant effects on a specific "decision node" that controls the emergence of neurons and glia from neural stem cells.

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Published In

Toxicology

DOI

EISSN

1879-3185

Publication Date

November 30, 2016

Volume

372

Start / End Page

42 / 51

Location

Ireland

Related Subject Headings

  • Toxicology
  • Tobacco Smoke Pollution
  • Receptors, GABA-A
  • Rats
  • Primary Cell Culture
  • Pregnancy
  • Nicotine
  • Nickel
  • Neurotoxins
  • Neurotoxicity Syndromes
 

Citation

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Slotkin, T. A., Skavicus, S., Card, J., Levin, E. D., & Seidler, F. J. (2016). Diverse neurotoxicants target the differentiation of embryonic neural stem cells into neuronal and glial phenotypes. Toxicology, 372, 42–51. https://doi.org/10.1016/j.tox.2016.10.015
Slotkin, Theodore A., Samantha Skavicus, Jennifer Card, Edward D. Levin, and Frederic J. Seidler. “Diverse neurotoxicants target the differentiation of embryonic neural stem cells into neuronal and glial phenotypes.Toxicology 372 (November 30, 2016): 42–51. https://doi.org/10.1016/j.tox.2016.10.015.
Slotkin TA, Skavicus S, Card J, Levin ED, Seidler FJ. Diverse neurotoxicants target the differentiation of embryonic neural stem cells into neuronal and glial phenotypes. Toxicology. 2016 Nov 30;372:42–51.
Slotkin, Theodore A., et al. “Diverse neurotoxicants target the differentiation of embryonic neural stem cells into neuronal and glial phenotypes.Toxicology, vol. 372, Nov. 2016, pp. 42–51. Pubmed, doi:10.1016/j.tox.2016.10.015.
Slotkin TA, Skavicus S, Card J, Levin ED, Seidler FJ. Diverse neurotoxicants target the differentiation of embryonic neural stem cells into neuronal and glial phenotypes. Toxicology. 2016 Nov 30;372:42–51.
Journal cover image

Published In

Toxicology

DOI

EISSN

1879-3185

Publication Date

November 30, 2016

Volume

372

Start / End Page

42 / 51

Location

Ireland

Related Subject Headings

  • Toxicology
  • Tobacco Smoke Pollution
  • Receptors, GABA-A
  • Rats
  • Primary Cell Culture
  • Pregnancy
  • Nicotine
  • Nickel
  • Neurotoxins
  • Neurotoxicity Syndromes