N-methyl-D-aspartate receptor agonists modulate homocysteine-induced developmental abnormalities

T. H. Rosenquist, A. M. Schneider, D. T. Monaghan

Research output: Contribution to journalArticle

50 Citations (Scopus)

Abstract

We showed previously that the induction of neural crest (NC) and neural tube (NT) defects is a general property of N-methyl-D-aspartate receptor (NMDAR) antagonists. Since homocysteine induces NC and NT defects and can also act as an NMDAR antagonist, we hypothesized that the mechanism of homocysteine-induced developmental defects is mediated by competitive inhibition of the NMDAR by homocysteine. If this hypothesis is correct, homocysteine-induced defects will be reduced by NMDAR agonists. To test the hypothesis, we treated chicken embryos during the process of neural tube closure with sufficient homocysteine thiolactone to induce NC and NT defects in ~40% of survivors or with homocysteine thiolactone in combination with each of a selected set of NMDAR agonists in 0.05-5000 nmol doses. Glutamate site agonists selected were L-glutamate and N-methyl-D-aspartate. Glycine site agonists were glycine, D-cycloserine, and aminocyclopropane-carboxylic acid. Glycine was the most effective overall, reducing defects significantly at two different doses (each P > 0.001). These results support the hypothesis that homocysteine may affect NC and NT development by its ability to inhibit the NMDAR. One potentially important consequence of this putative mechanism is that homocysteine may interact synergistically with other NMDAR antagonists to enhance its effect on development.

Original languageEnglish (US)
Pages (from-to)1523-1531
Number of pages9
JournalFASEB Journal
Volume13
Issue number12
StatePublished - Sep 8 1999

Fingerprint

homocysteine
abnormal development
Homocysteine
aspartic acid
N-Methyl-D-Aspartate Receptors
agonists
Neural Crest
receptors
neural crest
Defects
Neural Tube Defects
neural tube defects
Glycine
Neural Tube
antagonists
glutamates
Cycloserine
cycloserine
Excitatory Amino Acid Agonists
N-Methylaspartate

Keywords

  • Neural crest defects
  • Neural tube defects
  • Orofacial defects
  • Prevention

ASJC Scopus subject areas

  • Biotechnology
  • Biochemistry
  • Molecular Biology
  • Genetics

Cite this

N-methyl-D-aspartate receptor agonists modulate homocysteine-induced developmental abnormalities. / Rosenquist, T. H.; Schneider, A. M.; Monaghan, D. T.

In: FASEB Journal, Vol. 13, No. 12, 08.09.1999, p. 1523-1531.

Research output: Contribution to journalArticle

Rosenquist, T. H. ; Schneider, A. M. ; Monaghan, D. T. / N-methyl-D-aspartate receptor agonists modulate homocysteine-induced developmental abnormalities. In: FASEB Journal. 1999 ; Vol. 13, No. 12. pp. 1523-1531.
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