Kapfhammer J P, Schwab M E
Brain Research Institute, University of Zurich, Switzerland.
Eur J Neurosci. 1994 Mar 1;6(3):403-11. doi: 10.1111/j.1460-9568.1994.tb00283.x.
In the normal central nervous system (CNS) the regional expression of the growth-associated protein GAP-43 is complementary to the pattern of myelination. This has led us to suspect that myelin-associated neurite growth inhibitors might contribute to the suppression of GAP-43 expression by suppressing sprouting and plastic changes of synaptic terminals in myelinated CNS areas. In order to study the relationship between myelination and GAP-43 expression more directly, we experimentally prevented myelination of the lumbar spinal cord of rats through neonatal X-irradiation. The GAP-43 protein expression in myelin-free spinal cords was analysed by immunohistochemistry and immunoblotting and compared to age-matched normal spinal cords. We found that in the absence of myelination, GAP-43 expression is strongly increased in the spinal cord of 4-week-old rats. GAP-43 was most strongly expressed in descending fibre tracts, where expression in the normal spinal cord is very low. In grey matter the typical regional pattern of GAP-43 expression did not develop; instead GAP-43 expression was high in all regions of the spinal cord. The overall pattern of myelination and GAP-43 expression in the myelin-free cord resembled that of early postnatal stages. This indicates that the regional down-regulation of GAP-43 expression during normal postnatal development did not occur in the myelin-free areas. Our results support the hypothesis that neurite growth inhibitors from oligodendrocytes and CNS myelin suppress sprouting and plastic changes of synaptic terminals in the normal CNS and are thereby involved in regulating the stability of neural connections.
在正常的中枢神经系统（CNS）中，生长相关蛋白GAP - 43的区域表达与髓鞘形成模式互补。这使我们怀疑髓鞘相关的神经突生长抑制剂可能通过抑制有髓鞘的CNS区域中突触终末的发芽和可塑性变化，来抑制GAP - 43的表达。为了更直接地研究髓鞘形成与GAP - 43表达之间的关系，我们通过新生大鼠X射线照射实验性地阻止了大鼠腰脊髓的髓鞘形成。通过免疫组织化学和免疫印迹分析了无髓鞘脊髓中GAP - 43蛋白的表达，并与年龄匹配的正常脊髓进行了比较。我们发现，在没有髓鞘形成的情况下，4周龄大鼠脊髓中GAP - 43的表达强烈增加。GAP - 43在下行纤维束中表达最强，而在正常脊髓中该区域的表达非常低。在灰质中，GAP - 43表达的典型区域模式并未形成；相反，脊髓所有区域的GAP - 43表达都很高。无髓鞘脊髓中髓鞘形成和GAP - 43表达的总体模式类似于出生后早期阶段。这表明在正常出生后发育过程中GAP - 43表达的区域下调在无髓鞘区域并未发生。我们的结果支持这样的假设，即少突胶质细胞和CNS髓鞘中的神经突生长抑制剂在正常CNS中抑制突触终末的发芽和可塑性变化，从而参与调节神经连接的稳定性。
