REGULATION OF APOLIPOPROTEIN-E GENE-EXPRESSION AFTER INJURY OF THE RAT SCIATIC-NERVE

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 < 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 post‐transcriptional 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. Copyright © 1990 Wiley‐Liss, Inc.