Wrathall J R, Li W, Hudson L D
Neurobiology Division, Department of Cell Biology, Georgetown University, Washington, DC 20007, USA.
J Neurosci. 1998 Nov 1;18(21):8780-93. doi: 10.1523/JNEUROSCI.18-21-08780.1998.
After incomplete traumatic spinal cord injury (SCI), the spared tissue exhibits abnormal myelination that is associated with reduced or blocked axonal conductance. To examine the molecular basis of the abnormal myelination, we used a standardized rat model of incomplete SCI and compared normal uninjured tissue with that after contusion injury. We evaluated expression of mRNA for myelin proteins using in situ hybridization with oligonucleotide probes to proteolipid protein (PLP), the major protein in central myelin; myelin basic protein (MBP), a major component of central myelin and a minor component of peripheral myelin; and protein zero (P0), the major structural protein of peripheral myelin, as well as myelin transcription factor 1 (MYT1). We found reduced expression of PLP and MBP chronically after SCI in the dorsal, lateral, and ventral white matter both rostral and caudal to the injury epicenter. Detailed studies of PLP at 2 months after injury indicated that the density of expressing cells was normal but mRNA per cell was reduced. In addition, P0, normally restricted to the peripheral nervous system, was expressed both at the epicenter and in lesioned areas at least 4 mm rostral and caudal to it. Thus, after SCI, abnormal myelination of residual axons may be caused, at least in part, by changes in the transcriptional regulation of genes for myelin proteins and by altered distribution of myelin-producing cells. In addition, the expression of MYT1 mRNA and protein seemed to be upregulated after SCI in a pattern suggesting the presence of undifferentiated progenitor cells in the chronically injured cord.
在不完全性创伤性脊髓损伤（SCI）后，未受损组织会出现异常髓鞘形成，这与轴突传导减少或受阻有关。为了研究异常髓鞘形成的分子基础，我们使用了标准化的大鼠不完全性SCI模型，并将正常未损伤组织与挫伤损伤后的组织进行比较。我们使用与少突胶质细胞髓磷脂蛋白（PLP，中枢髓鞘的主要蛋白）、髓鞘碱性蛋白（MBP，中枢髓鞘的主要成分和外周髓鞘的次要成分）、蛋白零（P0，外周髓鞘的主要结构蛋白）以及髓鞘转录因子1（MYT1）的寡核苷酸探针进行原位杂交，评估髓鞘蛋白的mRNA表达。我们发现，在SCI后，损伤中心头侧和尾侧的背侧、外侧和腹侧白质中，PLP和MBP的表达长期减少。损伤后2个月对PLP的详细研究表明，表达细胞的密度正常，但每个细胞的mRNA减少。此外，通常局限于外周神经系统的P0在损伤中心以及损伤中心头侧和尾侧至少4毫米的损伤区域均有表达。因此，SCI后，残留轴突的异常髓鞘形成可能至少部分是由髓鞘蛋白基因转录调控的变化以及髓鞘生成细胞分布的改变引起的。此外，SCI后MYT1 mRNA和蛋白的表达似乎上调，其模式表明在慢性损伤的脊髓中存在未分化的祖细胞。
