LeBlanc A C, Poduslo J F
Department of Neurology, Mayo Clinic, Rochester, MN 55905.
J Neurosci Res. 1990 Feb;25(2):162-71. doi: 10.1002/jnr.490250203.
The expression of apolipoprotein E (apo E) is dramatically increased following peripheral nerve injury. This increased expression has been postulated to be negatively influenced by unknown mechanisms during subsequent axonal regeneration (Muller et al.: Science 228:499-501, 1985). The present study investigates the role of the regenerating axon in regulating apo E gene expression in two experimental paradigms which permit or prevent axonal regeneration in the adult rat sciatic nerve--the crush or permanent transection injuries. The nerves in these two models undergo axonal degeneration, demyelination, and Schwann cell proliferation; however, subsequent axonal regeneration and remyelination occur only in the distal segment of the crush-injured and not in the permanently transected nerve. The steady-state levels of apo E mRNA in both models increase sharply between 1 and 4 days and reach a maximum level at 12-14 days, which did not change significantly between 14 and 35 days after injury. No significant difference is observed in the steady-state levels of apo E mRNA between the crushed and permanently transected nerves as a function of time after injury. The steady-state protein level of apo E in the endoneurial segments initially increases, peaks at 14-21 days, and then decreases between 35 and 60 days after injury in both models. In contrast, the rate of newly translated and secreted apo E significantly increases by fourfold (P less than 0.005) between 35 and 60 days after permanent transection whereas it does not significantly differ at these times after crush injury. The increased rate of translation and secretion of apo E after transection compared to the constant rate observed after crush injury, together with the comparable steady-state levels of apo E mRNA and protein in both models, suggests translational or post-translational control, but not transcriptional and/or posttranscriptional control, by the regenerating axons. Furthermore, the increasing rate of biosynthesis and secretion of apo E after permanent transection concomitant with the decreasing steady-state levels of the protein suggests that apo E is either removed from the endoneurium or subsequently utilized or degraded by mechanisms that are independent from nerve regeneration.
周围神经损伤后，载脂蛋白E（apo E）的表达显著增加。据推测，在随后的轴突再生过程中，这种增加的表达受到未知机制的负面影响（Muller等人：《科学》228:499 - 501，1985）。本研究在两种实验范式中研究再生轴突在调节apo E基因表达中的作用，这两种范式允许或阻止成年大鼠坐骨神经的轴突再生——挤压或永久性横断损伤。这两种模型中的神经都会经历轴突变性、脱髓鞘和施万细胞增殖；然而，随后的轴突再生和髓鞘再生仅发生在挤压损伤的远端节段，而不会发生在永久性横断的神经中。两种模型中apo E mRNA的稳态水平在1至4天之间急剧增加，并在12 - 14天达到最高水平，在损伤后14至35天之间没有显著变化。在损伤后的不同时间点，挤压神经和永久性横断神经中apo E mRNA的稳态水平没有观察到显著差异。在两种模型中，神经内膜段中apo E的稳态蛋白水平最初升高，在14 - 21天达到峰值，然后在损伤后35至60天之间下降。相比之下，永久性横断后35至60天之间，新翻译和分泌的apo E速率显著增加了四倍（P小于0.005），而在挤压损伤后的这些时间点没有显著差异。与挤压损伤后观察到的恒定速率相比，横断后apo E翻译和分泌速率的增加，以及两种模型中apo E mRNA和蛋白的可比稳态水平，表明是再生轴突进行翻译或翻译后控制，而不是转录和/或转录后控制。此外，永久性横断后apo E生物合成和分泌速率的增加与蛋白稳态水平的降低同时出现，这表明apo E要么从神经内膜中被清除，要么随后被与神经再生无关的机制利用或降解。
