ALTERED EXPRESSION OF NEURONAL CELL-ADHESION MOLECULES INDUCED BY NERVE INJURY AND REPAIR

ALTERED EXPRESSION OF NEURONAL CELL-ADHESION MOLECULES INDUCED BY NERVE INJURY AND REPAIR
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DOI:
10.1083/jcb.103.3.929
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发表时间:
1986-09-01
影响因子:
7.8
通讯作者:
EDELMAN, GM
EDELMAN, GM
中科院分区:
生物学1区
文献类型:
--
作者:
DANILOFF, JK;LEVI, G;EDELMAN, GM

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周围神经损伤导致神经元和胶质细胞的短期和长期变化。在本研究中,免疫组化和免疫印迹分析被用来检查神经细胞粘附分子(N-CAM)和神经胶质细胞粘附分子(Ng-CAM)的表达在不同的部分功能相关的神经肌肉系统从骨骼肌延伸到脊髓周围神经损伤后。在成年鸡和小鼠坐骨神经压碎或横断后3至150 d采集组织学样品。在未受干扰的组织中,N-CAM和Ng-CAM都被发现在无髓轴突上,在较小程度上在雪旺细胞和有髓轴突上。仅在肌肉中发现N-CAM。失神经支配后,肌纤维表面、胞浆及肌纤维间质N-CAM含量短暂增加。(b)肌肉中正常N-CAM水平的恢复依赖于神经再支配;在慢性失神经状态下,N-CAM水平仍然很高。(c)压碎或切割神经后,病变周围区域的两种CAM的量都增加,N-CAM的主要形式从离散的Mr 140,000成分变成多分散的高分子量胚胎形式。抗N-CAM抗体染色的神经突起,雪旺细胞,和再生坐骨神经的神经束膜。抗Ng-CAM抗体标记远端残端的神经突、雪旺细胞和神经内膜管。(d)CAM分布的变化,观察到在背根神经节和脊髓后,神经被切断。受影响的背根神经节内的纤维更强烈地标记为两种CAM,并且受影响节段的脊髓腹角中的运动神经元在抗N-CAM和抗Ng-CAM的环形图案中的染色更强烈,而不是它们在病变对侧的对应物。与以前的研究(Rieger,F.,M. Grumet和G. M. Edelman,J. Cell Biol.101:285-293),这些数据表明神经元和神经胶质之间的局部信号可以调节再生期间脊髓和神经中的CAM表达,并且该活性可以调节肌肉中的N-CAM表达。本观察结果的相关性在这里与神经变性的既定事件,并提出了一些角色的CAM在再生事件。这种相关性可能在神经修复的研究中具有实际应用,特别是鉴于CAM在介导细胞-细胞粘附导致组织结构中的功能。
Peripheral nerve injury results in short-term and long-term changes in both neurons and glia. In the present study, immunohistological and immunoblot analyses were used to examine the expression of the neural cell adhesion molecule (N-CAM) and the neuron-glia cell adhesion molecule (Ng-CAM) within different parts of a functionally linked neuromuscular system extending from skeletal muscle to the spinal cord after peripheral nerve injury. Histological samples were taken from 3 to 150 d after crushing or transecting the sciatic nerve in adult chickens and mice. In unperturbed tissues, both N-CAM and Ng-CAM were found on nonmyelinated axons, and to a lesser extent on Schwann cells and myelinated axons. Only N-CAM was found on muscles. After denervation, the following changes were observed: (a) The amount of N-CAM in muscle fibers increased transiently on the surface and in the cytoplasm, and in interstitial spaces between fibers. (b) Restoration of normal N-CAM levels in muscle was dependent on reinnervation; in a chronically denervated state, N-CAM levels remained high. (c) After crushing or cutting the nerve, the amount of both CAMs increased in the area surrounding the lesion, and the predominant form of N-CAM changed from a discrete Mr 140,000 component to the polydisperse high molecular weight embryonic form. Anti-N-CAM antibodies stained neurites, Schwann cells, and the perineurium of the regenerating sciatic nerve. Anti-Ng-CAM antibodies labeled neurites, Schwann cells and the endoneurial tubes in the distal stump. (d) Changes in CAM distribution were observed in dorsal root ganglia and in the spinal cord only after the nerve was cut. The fibers within affected dorsal root ganglia were more intensely labeled for both CAMs, and the motor neurons in the ventral horn of the spinal cord of the affected segments were stained more intensely in a ring pattern by anti-N-CAM and anti-Ng-CAM than their counterparts on the side contralateral to the lesion. Taken together with the previous studies (Rieger, F., M. Grumet, and G. M. Edelman, J. Cell Biol. 101:285-293), these data suggest that local signals between neurons and glia may regulate CAM expression in the spinal cord and nerve during regeneration, and that activity may regulate N-CAM expression in muscle. Correlations of the present observations are made here with established events of nerve degeneration and suggest a number of roles for the CAMs in regenerative events. Such correlations may have practical applications in the study of nerve repair particularly in view of the function of CAMs in mediating cell-cell adhesion leading to tissue structures.