THE EXPRESSION OF THE LOW-AFFINITY NERVE GROWTH-FACTOR RECEPTOR IN LONG-TERM DENERVATED SCHWANN-CELLS

Schwann cells in the distal stump of injured peripheral nerves synthes ize the low affinity nerve growth factor receptor (p75). In this study we used short-term (1 week) and long-term (1-12 months) transected di stal sciatic nerves of rats to determine the variations of p75 express ion by using immunocytochemistry and in situ hybridization. Semi-quant itative analysis revealed that the synthesis of the protein product of the p75 gene is rapidly enhanced to reach a peak within the 1 month a fter denervation. After that it gradually decreased and was barely det ectable 6 months following denervation. Double immunocytochemistry for p75 and the S100 protein revealed that p75 immunoreactivity is confin ed to the Schwann cells. Quantitative analysis of our in situ hybridiz ation experiments revealed that the upregulation of the p75 mRNA paral lels the enhanced synthesis of the corresponding protein and reaches a peak within 1 month, which is maintained until the second month after the transection and declines thereafter to reach background levels at 4 months. The electron microscopic observations reveal that the incre ase in the number of nuclei in the distal stump belong to severely atr ophied Schwann cells and fibroblasts. Since the presence of p75 in the Schwann cells is necessary for reinnervation, our results indicate th at, based on the expression of p75, the Schwann cells will provide a m ost suitable environment for the regenerating axons up to the first mo nth. At later stages the ability of the Schwann cells to synthesize p7 5 and cell adhesion proteins such as N-CAM and GAP 43 decreases which may be one of the factors that contribute to poor functional recovery if the regenerating axons reach the distal stump after long periods of time. (C) 1997 Wiley-Liss, Inc.