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.
摘要:
开放性神经管缺陷(NTDs),例如脊髓膜膨出(MMC)是使人衰弱的,是中枢神经系统最常见的先天性缺陷。尽管它们具有明显的临床重要性,针对这些缺陷的现有早期产前诊断选择仍然有限.使用公认的维甲酸诱导的MMC在胎儿大鼠中建立的模型,我们发现神经聚糖和磷酸聚糖,发育中的神经系统分泌的硫酸软骨素蛋白聚糖,被释放到显示脊髓缺陷的胎鼠的羊水(AF)中。与正常对照相比,在妊娠早期的MMC胎儿中检测到神经递质和磷酸聚糖的房颤水平升高,并且在MMC进展期间继续升高。在近期胎儿中达到最高水平。在MMC胎儿的AF中鉴定出的神经聚糖和磷酸聚糖的分子形式与在MMC脊髓中发现的分子形式在质量上相似。总之,这是首次报告证明MMC胎儿AF中存在神经聚糖和磷酸聚糖。MMC胎儿AF中神经聚糖和磷酸聚糖水平升高的鉴定提供了两种前瞻性生物标志物,具有早期产前诊断开放性NTDs的潜力。