Kalil K, Skene J H
J Neurosci. 1986 Sep;6(9):2563-70. doi: 10.1523/JNEUROSCI.06-09-02563.1986.
Axons of the adult mammalian CNS typically fail to regenerate after injury. Among the hypotheses to account for this failure is the proposition that certain axonal proteins necessary for axon growth are expressed in much greater abundance in developing than in mature neurons, and that these proteins are not reinduced after injury to mature axons (Skene and Willard, 1981b). In the present experiments, we have found that hamster pyramidal tract neurons synthesize an acidic, 43K protein that is transported into growing axons during the first 2 weeks of postnatal development, and then declines at least an order of magnitude by the fourth postnatal week. The decline in synthesis of the 43K protein coincides with the cessation of pyramidal tract axon elongation. This protein resembles a "growth-associated protein," GAP-43, which is induced during regeneration of CNS axons in lower vertebrates. The 43K protein in hamster pyramidal tract neurons is not reinduced after axotomy in adult animals, which correlates with the failure of the injured axons to regenerate. Injury to neonatal pyramidal tract axons does not reverse or delay the decline in 43K protein synthesis. This is consistent with previous findings (Kalil and Reh, 1982) that pyramidal tract axons regrow for only a brief period after neonatal injury. Taken together, these results lend support to the hypothesis that synthesis of GAP-43 is important for axon growth in development and regeneration.
成年哺乳动物中枢神经系统的轴突在受伤后通常无法再生。关于这种再生失败的假说之一是，轴突生长所必需的某些轴突蛋白在发育中的神经元中表达量比成熟神经元中要高得多，并且这些蛋白在成熟轴突受伤后不会重新诱导表达（Skene和Willard，1981b）。在本实验中，我们发现仓鼠锥体束神经元合成一种酸性的43K蛋白，该蛋白在出生后发育的前两周被转运到生长中的轴突中，然后在出生后第四周至少下降一个数量级。43K蛋白合成的下降与锥体束轴突伸长的停止相吻合。这种蛋白类似于一种“生长相关蛋白”，即GAP - 43，它在低等脊椎动物中枢神经系统轴突再生过程中被诱导表达。成年动物轴突切断后，仓鼠锥体束神经元中的43K蛋白不会重新诱导表达，这与受伤轴突无法再生相关。新生锥体束轴突损伤不会逆转或延迟43K蛋白合成的下降。这与之前的研究结果（Kalil和Reh，1982）一致，即新生损伤后锥体束轴突仅在短时间内再生。综上所述，这些结果支持了GAP - 43的合成对发育和再生过程中的轴突生长很重要这一假说。
