Neurotrophin-3 and brain-derived neurotrophic factor induce oligodendrocyte proliferation and myelination of regenerating axons in the contused adult rat spinal cord
Neurotrophin-3 and brain-derived neurotrophic factor induce oligodendrocyte proliferation and myelination of regenerating axons in the contused adult rat spinal cord
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DOI：
10.1523/jneurosci.18-14-05354.1998
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发表时间：
1998-07-15
影响因子：
5.3
通讯作者：
Gage, FH
中科院分区：
文献类型：
--
作者：
McTigue, DM;Horner, PJ;Gage, FH
脊髓损伤（SCI）后的功能丧失部分是由于创伤后残存的轴突脱髓鞘引起的。神经营养因子已被证明在体外诱导少突胶质形成，但这些因素在体内对少突胶质细胞增殖和髓鞘形成的刺激尚未被研究。我们试图确定神经营养素是否可以诱导成年大鼠脊髓损伤后再生轴突的新少突胶质细胞的形成和髓鞘形成。在这项研究中，将产生神经营养因子-3 （NT-3）、脑源性神经营养因子（BDNF）、睫状神经营养因子、神经生长因子、碱性成纤维细胞生长因子或p -半乳糖苷酶的成纤维细胞（对照移植物）亚急性移植到损伤的成年大鼠脊髓中。损伤后10周，所有移植物均含有轴突。然而，NT-3和BDNF移植物比对照或其他产生生长因子的移植物含有更多的轴突。此外，在NT-3和BDNF移植中检测到更多的髓鞘碱性蛋白阳性谱，这表明在这些产生神经营养因子的移植物中，生长轴突的髓鞘形成增强。为了确定髓鞘生成增强是否与少突胶质细胞系细胞增殖增加有关，使用溴脱氧尿苷（BrdU）标记分裂细胞。NT-3和BDNF移植物比对照组含有更多brdu阳性少突胶质细胞。这些新的少突胶质细胞与向内生长的髓鞘轴突的关联表明，NT-3和bdnf诱导的髓鞘形成至少部分是由于少突胶质细胞谱系细胞的扩增，最有可能是内源性少突胶质细胞祖细胞。这些发现可能对慢性脱髓鞘疾病或中枢神经系统损伤具有重要意义。
Functional loss after spinal cord injury (SCI) is caused, in part, by demyelination of axons surviving the trauma. Neurotrophins have been shown to induce oligodendrogliagenesis in vitro, but stimulation of oligodendrocyte proliferation and myelination by these factors in vivo has not been examined. We sought to determine whether neurotrophins can induce the formation of new oligodendrocytes and myelination of regenerating axons after SCI in adult rats. In this study, fibroblasts producing neurotrophin-3 (NT-3), brain-derived neurotrophic factor (BDNF), ciliary neurotrophic factor, nerve growth factor, basic fibroblast growth factor, or P-galactosidase (control grafts) were transplanted subacutely into the contused adult rat spinal cord. At 10 weeks after injury, all transplants contained axons. NT-3 and BDNF grafts, however, contained significantly more axons than control or other growth factor-producing grafts. In addition, significantly more myelin basic protein-positive profiles were detected in NT-3 and BDNF transplants, suggesting enhanced myelination of ingrowing axons within these neurotrophin-producing grafts. To determine whether augmented myelinogenesis was associated with increased proliferation of oligodendrocyte lineage cells, bromodeoxyuridine (BrdU) was used to label dividing cells. NT-3 and BDNF grafts contained significantly more BrdU-positive oligodendrocytes than controls. The association of these new oligodendrocytes with ingrowing myelinated axons suggests that NT-3- and BDNF-induced myelinogenesis resulted, at least in part, from expansion of oligodendrocyte lineage cells, most likely the endogenous oligodendrocyte progenitors. These findings may have significant implications for chronic demyelinating diseases or CNS injuries.