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Unrelated developmental neurotoxicants elicit similar transcriptional profiles for effects on neurotrophic factors and their receptors in an in vitro model.

Publication ,  Journal Article
Slotkin, TA; Seidler, FJ; Fumagalli, F
Published in: Neurotoxicol Teratol
2010

Diverse developmental neurotoxicants can often produce similar functional and behavioral outcomes. We examined an organophosphate pesticide (diazinon), an organochlorine pesticide (dieldrin) and a metal (Ni(2+)) for effects on the expression of neurotrophic factors and their receptors and modulators in differentiating PC12 cells, an in vitro model of neuronal development. Each agent was introduced at 30 microM for 24 or 72 h, treatments devoid of cytotoxicity. Using microarrays, we examined the mRNAs encoding members of the fibroblast growth factor (fgf) family, the neurotrophins (ntfs), brain-derived neurotrophic factor (bdnf), nerve growth factor (ngf), the wnt and fzd gene families, and the receptors and modulators for each class. All three agents evoked highly concordant patterns of effects on genes encoding the fgf family, whereas the correlations were poor for the group comprising bdnf, ngf and their respective receptors. For wnt, fzd and their receptors/modulators, the relationships between diazinon and dieldrin were highly concordant, whereas the effect of Ni(2+) was less similar, albeit still significantly correlated with the others. Our results show that otherwise disparate developmental neurotoxicants converge on common sets of neurotrophic pathways known to control neuronal differentiation, likely contributing to similarities in functional outcomes. Further, cell culture models can provide a useful initial screen to identify members of a given class of compounds that may be greater or lesser risks for developmental neurotoxicity, or to provide an indication of agents in different classes that might produce similar effects.

Duke Scholars

Published In

Neurotoxicol Teratol

DOI

EISSN

1872-9738

Publication Date

2010

Volume

32

Issue

1

Start / End Page

42 / 51

Location

United States

Related Subject Headings

  • Wnt Proteins
  • Trace Elements
  • Toxicology
  • Rats
  • PC12 Cells
  • Nickel
  • Neurons
  • Nerve Growth Factor
  • Insecticides
  • Gene Expression Regulation, Developmental
 

Citation

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Slotkin, T. A., Seidler, F. J., & Fumagalli, F. (2010). Unrelated developmental neurotoxicants elicit similar transcriptional profiles for effects on neurotrophic factors and their receptors in an in vitro model. Neurotoxicol Teratol, 32(1), 42–51. https://doi.org/10.1016/j.ntt.2008.11.006
Slotkin, Theodore A., Frederic J. Seidler, and Fabio Fumagalli. “Unrelated developmental neurotoxicants elicit similar transcriptional profiles for effects on neurotrophic factors and their receptors in an in vitro model.Neurotoxicol Teratol 32, no. 1 (2010): 42–51. https://doi.org/10.1016/j.ntt.2008.11.006.
Slotkin, Theodore A., et al. “Unrelated developmental neurotoxicants elicit similar transcriptional profiles for effects on neurotrophic factors and their receptors in an in vitro model.Neurotoxicol Teratol, vol. 32, no. 1, 2010, pp. 42–51. Pubmed, doi:10.1016/j.ntt.2008.11.006.

Published In

Neurotoxicol Teratol

DOI

EISSN

1872-9738

Publication Date

2010

Volume

32

Issue

1

Start / End Page

42 / 51

Location

United States

Related Subject Headings

  • Wnt Proteins
  • Trace Elements
  • Toxicology
  • Rats
  • PC12 Cells
  • Nickel
  • Neurons
  • Nerve Growth Factor
  • Insecticides
  • Gene Expression Regulation, Developmental