Related Experiment Videos
N-methyl-D-aspartate receptor agonists modulate homocysteine-induced developmental abnormalities
T H Rosenquist1, A M Schneider, D T Monogham
1University of Nebraska Medical Center, Omaha, Nebraska 68198-6395, USA. throsenq@unmc.edu
Summary
Homocysteine causes neural crest and tube defects by blocking N-methyl-D-aspartate receptors (NMDARs). NMDAR agonists, especially glycine, significantly reduced these developmental defects in chicken embryos.
Area of Science:
- Developmental biology
- Neuroscience
- Pharmacology
Background:
- N-methyl-D-aspartate receptor (NMDAR) antagonists are known to induce neural crest (NC) and neural tube (NT) defects.
- Homocysteine is implicated in developmental defects and acts as an NMDAR antagonist.
Purpose of the Study:
- To investigate if homocysteine-induced developmental defects are mediated by NMDAR inhibition.
- To determine if NMDAR agonists can prevent homocysteine-induced NC and NT defects.
Main Methods:
- Chicken embryos were treated with homocysteine thiolactone to induce defects.
- Embryos were co-treated with homocysteine thiolactone and various NMDAR agonists (glutamate, NMDA, glycine, D-cycloserine, ACC).
- The incidence of NC and NT defects was assessed.
Main Results:
- Homocysteine thiolactone induced NC and NT defects in approximately 40% of surviving embryos.
- Co-administration of NMDAR agonists, particularly glycine, significantly reduced the incidence of these defects.
- Glycine demonstrated significant protective effects at two different doses.
Conclusions:
- The findings support the hypothesis that homocysteine impairs NC and NT development by inhibiting NMDARs.
- Homocysteine may synergistically interact with other NMDAR antagonists, exacerbating developmental effects.