ZFIN ID: ZDB-PUB-140513-48
Overdose of D-serine Induces Movement Disorder and Neuromuscular Changes of Zebrafish Larvae
Chen, X.G., Wang, Y.H., Wen, C.C., Chen, Y.H.
Date: 2014
Source: Journal of Toxicologic Pathology   27: 19-24 (Journal)
Registered Authors: Chen, Yau-Hung
Keywords: D-serine, NMDA receptor, developmental toxicity
MeSH Terms: none
PubMed: 24791063 Full text @ J. Toxicol. Pathol.
D-serine is a well-known activator of N-methyl-D-aspartate receptors; however, little is known about the teratogenic effects of D-serine overdose during early embryonic development. Here, we used zebrafish as a model to test toxicity and teratogenicity, since they have transparent eggs, making the organogenesis of zebrafish embryos easier to be observed. After D-serine injection (100-1000 ppm), the most evident defective phenotypes were bent trunk phenotypes, including malformed somite boundary, twisted body axis and shorter body length. As the injection dosages increased, the rates of embryos with bent trunk phenotypes decreased (0% for 0 ppm, n=573; 59.9~84.3% for 100-1000 ppm of D-serine, n=383-451). In addition, D-serine-injected embryos exhibited significantly reduced the frequencies of spontaneous in-chorion contraction (21.7 for 0 ppm vs. 18.3-0.9 for 100-1000 ppm D-serine, n=30) in comparison with mock-treated controls (0 ppm). Subtle changes are easily observed by staining with specific monoclonal antibodies F59, Znp1, Zn5 and α-bungarotoxin to detect morphological changes in muscle fibers, primary motor axons, secondary motor axon projections and neuromuscular junctions, respectively. Our data show that overdose of D-serine leads to misalignment of muscle fibers and motor neuron defects, especially secondary motor neuron axonal growth defects.