Identification of Neurocan and Phosphacan as Early Biomarkers for Open Neural Tube Defects

Abstract

Open neural tube defects (NTDs) such as myelomeningocele (MMC) are debilitating and the most common congenital defects of the central nervous system. Despite their apparent clinical importance, the existing early prenatal diagnostic options for these defects remain limited. Using a well-accepted retinoic-acid-induced model of MMC established in fetal rats, we discovered that neurocan and phosphacan, the secreted chondroitin sulfate proteoglycans of the developing nervous system, are released into the amniotic fluid (AF) of fetal rats displaying spinal cord defects. In contrast to normal controls, elevated AF levels of neurocan and phosphacan were detected in MMC fetuses early in gestation and continued to increase during MMC progression, reaching the highest level in near-term fetuses. The molecular forms of neurocan and phosphacan identified in the AF of MMC fetuses and those found in MMC spinal cords were qualitatively similar. In summary, this is the first report demonstrating the presence of neurocan and phosphacan in the AF of MMC fetuses. The identification of elevated levels of neurocan and phosphacan in the AF of MMC fetuses provides two prospective biomarkers with the potential for early prenatal diagnosis of open NTDs.