Wang Xingxing, Chun Soo-Jin, Treloar Helen, Vartanian Timothy, Greer Charles A, Strittmatter Stephen M
Departments of Neurology and Neurosurgery and Section of Neurobiology, Yale University School of Medicine, New Haven, Connecticut 06510, USA.
J Neurosci. 2002 Jul 1;22(13):5505-15. doi: 10.1523/JNEUROSCI.22-13-05505.2002.
Axon regeneration in the adult CNS is limited by the presence of inhibitory proteins. An interaction of Nogo on the oligodendrocyte surface with Nogo-66 Receptor (NgR) on axons has been suggested to play an important role in limiting axonal growth. Here, we compare the localization of these two proteins immunohistochemically as a test of this hypothesis. Throughout much of the adult CNS, Nogo-A is detected on oligodendrocyte processes surrounding myelinated axons, including areas of axon-oligodendrocyte contact. The NgR protein is detected selectively in neurons and is present throughout axons, indicating that Nogo-A and its receptor are juxtaposed along the course of myelinated fibers. NgR protein expression is restricted to postnatal neurons and their axons. In contrast, Nogo-A is observed in myelinating oligodendrocytes, embryonic muscle, and neurons, suggesting that Nogo-A has additional physiologic roles unrelated to NgR binding. After spinal cord injury, Nogo-A is upregulated to a moderate degree, whereas NgR levels are maintained at constant levels. Taken together, these data confirm the apposition of Nogo ligand and NgR receptor in situations of limited axonal regeneration and support the hypothesis that this system regulates CNS axonal plasticity and recovery from injury.
成年中枢神经系统中的轴突再生受到抑制性蛋白的限制。少突胶质细胞表面的Nogo与轴突上的Nogo-66受体（NgR）之间的相互作用被认为在限制轴突生长中起重要作用。在此，我们通过免疫组织化学方法比较这两种蛋白的定位，以检验这一假说。在成年中枢神经系统的大部分区域，在围绕有髓轴突的少突胶质细胞突起上可检测到Nogo-A，包括轴突与少突胶质细胞接触的区域。NgR蛋白在神经元中被选择性检测到，并且存在于整个轴突中，这表明Nogo-A及其受体在有髓纤维的行程中并列存在。NgR蛋白表达仅限于出生后的神经元及其轴突。相比之下，在髓鞘形成的少突胶质细胞、胚胎肌肉和神经元中观察到Nogo-A，这表明Nogo-A具有与NgR结合无关的其他生理作用。脊髓损伤后，Nogo-A适度上调，而NgR水平保持恒定。综上所述，这些数据证实了在轴突再生受限的情况下Nogo配体和NgR受体的并列存在，并支持该系统调节中枢神经系统轴突可塑性和损伤后恢复的假说。
