Grever W E, Weidenheim K M, Tricoche M, Rashbaum W K, Lyman W D
Department of Pathology, Albert Einstein College of Medicine, Bronx, New York, USA.
J Neurosci Res. 1997 Feb 1;47(3):332-40. doi: 10.1002/(sici)1097-4547(19970201)47:3<332::aid-jnr11>3.0.co;2-3.
A comprehensive evaluation of myelination during normal human development is essential to understand the pathology of congenital diseases of white matter. The present study establishes quantitative values for normal oligodendrocyte-specific gene expression during the early stages of myelination in the human fetal spinal cord. Complementary techniques of Northern and immunoblotting were used to determine relative amounts of oligodendrocyte-specific mRNAs and proteins between 12 and 24 gestational weeks. Values were determined for myelin basic protein, 2',3'-cyclic nucleotide 3'-phosphodiesterase, and proteolipid protein. The relative amount of myelin-associated glycoprotein mRNA was also estimated. To compare gene expression between glial cell types, the relative amounts of mRNA and protein were determined for glial fibrillary acidic protein (GFAP), a cell-type specific marker for astrocytes. All oligodendrocyte-specific genes expressed similar developmental kinetics. Between 12 and 15 gestational weeks, less than a five-fold increase was detected in the expression of these genes and their protein products. Between 15 and 22 gestational weeks, the relative amounts of mRNA and protein for the myelin genes increased more than 80-fold. The kinetics of GFAP expression were similar to those of the myelin-associated genes. Absolute values for the increase in mass of the human fetal spinal cord were also obtained. These results provide data that may aid in the neuropathologic assessment and characterization of myelin disorders in the preterm, neonatal, and pediatric spinal cord.
全面评估正常人类发育过程中的髓鞘形成对于理解先天性白质疾病的病理学至关重要。本研究确定了人类胎儿脊髓髓鞘形成早期少突胶质细胞特异性基因表达的定量值。采用Northern印迹和免疫印迹的互补技术来测定妊娠12至24周期间少突胶质细胞特异性mRNA和蛋白质的相对含量。测定了髓鞘碱性蛋白、2',3'-环核苷酸3'-磷酸二酯酶和蛋白脂蛋白的值。还估计了髓鞘相关糖蛋白mRNA的相对含量。为了比较不同神经胶质细胞类型之间的基因表达,测定了星形胶质细胞的细胞类型特异性标志物胶质纤维酸性蛋白(GFAP)的mRNA和蛋白质的相对含量。所有少突胶质细胞特异性基因均表现出相似的发育动力学。在妊娠12至15周之间,这些基因及其蛋白质产物的表达增加不到五倍。在妊娠15至22周之间,髓鞘基因的mRNA和蛋白质的相对含量增加了80倍以上。GFAP表达的动力学与髓鞘相关基因的相似。还获得了人类胎儿脊髓质量增加的绝对值。这些结果提供的数据可能有助于对早产、新生儿和小儿脊髓的髓鞘疾病进行神经病理学评估和特征描述。