Influence of the axotomy to cell body distance in rat rubrospinal and spinal motoneurons: Differential regulation of GAP-43, tubulins, and neurofilament-M
Influence of the axotomy to cell body distance in rat rubrospinal and spinal motoneurons: Differential regulation of GAP-43, tubulins, and neurofilament-M
复制标题
DOI：
10.1002/(sici)1096-9861(19991129)414:4
复制
发表时间：
1999-11-29
影响因子：
2.5
通讯作者：
Tetzlaff, W
中科院分区：
文献类型：
--
作者：
Fernandes, KJL;Fan, DP;Tetzlaff, W
轴突切断的运动神经元再生其轴突，无论轴突切断是否发生在其细胞体的近端或远端。与此相反，红核脊髓轴突再生到周围神经移植后，已检测到颈部，但胸部红核脊髓束损伤后。通过使用原位杂交（ISH）结合可靠的逆行追踪方法，我们比较了再生相关基因的表达后，近端和远端轴突切断脊髓运动神经元与红核脊髓神经元。无论是在髂嵴（近端）还是在腘窝（远端）进行轴突切断，坐骨运动神经元的生长相关蛋白43（GAP-43）（增加10- 20倍）和神经丝M（减少60-85%）的ISH信号都发生了高度显著的变化。相比之下，微管蛋白ISH信号仅在近端轴突切断后显著增加（3- 5倍增加）。为了比较这些基因表达的变化与轴突切断的红核脊髓神经元，红核脊髓束在脊髓的颈部（近端）或胸部（远端）水平横断。颈轴突切断的红核脊髓神经元表现出3 - 5倍的ISH信号增加GAP-43和微管蛋白（仅短暂）和75%的神经元-M减少。与此形成鲜明对比的是，胸神经切断术只有边际效应。周围神经移植植入脊髓损伤部位后，用敏感的逆行示踪剂Fluoro-Gold逆行标记仅在颈神经切断后识别再生的红核脊髓神经元。此外，红核脊髓神经元特异性再生到移植物肥大，表达高水平的GAP-43和微管蛋白。两者合计，这些数据支持的概念，即使中枢神经系统（CNS）轴突与一个允许/支持的环境，适当的细胞体损伤的反应是CNS轴突再生的先决条件。(C)1999 Wiley利斯公司
Axotomized motoneurons regenerate their axons regardless of whether axotomy occurs proximally or distally from their cell bodies. In contrast, regeneration of rubrospinal axons into peripheral nerve grafts has been detected after cervical but not after thoracic injury of the rubrospinal tract. By using in situ hybridization (ISH) combined with reliable retrograde tracing methods, we compared regeneration-associated gene expression after proximal and distal axotomy in spinal motoneurons versus rubrospinal neurons. Regardless of whether they were axotomized at the iliac crest (proximal) or popliteal fossa (distal), sciatic motoneurons underwent highly pronounced changes in ISH signals for Growth Associated Protein 43 (GAP-43) (10-20x increase) and neurofilament M (60-85% decrease). In contrast, tubulin ISH signals substantially increased only after proximal axotomy (3-5x increase). To compare these changes in gene expression with those of axotomized rubrospinal neurons, the rubrospinal tract was transected at the cervical (proximal) or thoracic (distal) levels of the spinal cord. Cervically axotomized rubrospinal neurons showed three- to fivefold increases in ISH signals for GAP-43 and tubulins (only transient) and a 75% decrease for neurofilament-M. In sharp contrast, thoracic axotomy had only marginal effects. After implantation of peripheral nerve transplants into the spinal cord injury sites, retrograde labeling with the sensitive retrograde tracer Fluoro-Gold identified regenerating rubrospinal neurons only after cervical axotomy. Furthermore, rubrospinal neurons specifically regenerating into the transplants were hypertrophied and expressed high levels of GAP-43 and tubulins. Taken together, these data support the concept that, even if central nervous system (CNS) axons are presented with a permissive/supportive environment, appropriate cell body responses to injury are a prerequisite for CNS axonal regeneration. (C) 1999 Wiley Liss, Inc.