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Nicotine evokes cell death in embryonic rat brain during neurulation.

Publication ,  Journal Article
Roy, TS; Andrews, JE; Seidler, FJ; Slotkin, TA
Published in: J Pharmacol Exp Ther
December 1998

Maternal cigarette smoking during pregnancy represents the most prevalent exposure to a suspected neuroteratogen, nicotine. Although animal models have demonstrated brain cell loss and synaptic abnormalities after prenatal nicotine exposure, the multiple effects of nicotine on the maternal-fetal unit make it difficult to prove that nicotine itself is a neuroteratogen. In the current study, whole rat embryo culture was used to study the effects of nicotine at the neural tube stage of development. Beginning on embryonic day 9.5, embryos were exposed to 1, 10 or 100 microM nicotine. After 48 hr, embryos were examined for dysmorphogenesis and were then processed for light microscopic examination of the neuroepithelium. Examination of the forebrain, midbrain and hindbrain regions revealed extensive cytotoxicity, evidenced by cytoplasmic vacuolation, enlargement of intercellular spaces and a sharply increased incidence of pyknotic/apoptotic cells. These alterations were evident in the absence of generalized dysmorphogenesis and were detectable even at the lowest concentration of nicotine. At the highest concentration, abnormalities were present in the majority of cells. Superimposed on cell damage, we found an increase in mitotic figures. Although enhanced mitosis could represent partial compensation for cell loss, the regional selectivity and concentration dependence of the mitogenic effect differed significantly from that of cell death, suggesting separable mechanisms. The present results support the view that nicotine is a neuroteratogen, specifically targeting brain development at concentrations below the threshold for dysmorphogenesis.

Duke Scholars

Published In

J Pharmacol Exp Ther

ISSN

0022-3565

Publication Date

December 1998

Volume

287

Issue

3

Start / End Page

1136 / 1144

Location

United States

Related Subject Headings

  • Teratogens
  • Receptors, Nicotinic
  • Rats
  • Pharmacology & Pharmacy
  • Organ Culture Techniques
  • Nicotine
  • Neural Crest
  • Mitosis
  • Gestational Age
  • Female
 

Citation

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Roy, T. S., Andrews, J. E., Seidler, F. J., & Slotkin, T. A. (1998). Nicotine evokes cell death in embryonic rat brain during neurulation. J Pharmacol Exp Ther, 287(3), 1136–1144.
Roy, T. S., J. E. Andrews, F. J. Seidler, and T. A. Slotkin. “Nicotine evokes cell death in embryonic rat brain during neurulation.J Pharmacol Exp Ther 287, no. 3 (December 1998): 1136–44.
Roy TS, Andrews JE, Seidler FJ, Slotkin TA. Nicotine evokes cell death in embryonic rat brain during neurulation. J Pharmacol Exp Ther. 1998 Dec;287(3):1136–44.
Roy, T. S., et al. “Nicotine evokes cell death in embryonic rat brain during neurulation.J Pharmacol Exp Ther, vol. 287, no. 3, Dec. 1998, pp. 1136–44.
Roy TS, Andrews JE, Seidler FJ, Slotkin TA. Nicotine evokes cell death in embryonic rat brain during neurulation. J Pharmacol Exp Ther. 1998 Dec;287(3):1136–1144.

Published In

J Pharmacol Exp Ther

ISSN

0022-3565

Publication Date

December 1998

Volume

287

Issue

3

Start / End Page

1136 / 1144

Location

United States

Related Subject Headings

  • Teratogens
  • Receptors, Nicotinic
  • Rats
  • Pharmacology & Pharmacy
  • Organ Culture Techniques
  • Nicotine
  • Neural Crest
  • Mitosis
  • Gestational Age
  • Female