EFFECTS OF DELAYED RE-INNERVATION ON THE EXPRESSION OF C-ERBB RECEPTORS BY CHRONICALLY DENERVATED RAT SCHWANN-CELLS IN-VIVO

We propose that chronically denervated Schwann cells may be less able to respond to axonal signals than their acutely denervated counterpart s, and that this lack of sensitivity may be one reason why axons fail to regenerate into chronically denervated nerve stumps. To test this p roposal we have used in situ hybridization, and quantitative and quali tative immunohistochemistry to compare the expression of c-erbB2 and c -erbB4 receptors in Schwann cells denervated for up to 6 months in viv o, with that seen in Schwann cells denervated for similar periods of t ime but then exposed to regenerating axons. The results were correlate d with the extent of axonal regeneration in each experimental group as assessed from transverse sections which had been double-immunolabelle d using anti S-100 and anti-beta tubulin III antibodies. Since c-erbBs are receptors for neuronally derived neuregulins we probed the approp riate axotomised DRG neurons for expression of CGF2 mRNA. When the den ervated distal stumps were anastomosed to acutely transected proximal stumps, GGF expression in DRGs increased transiently during the first week: we assume that secreted GGF2 derived from regrowing axon sprouts would have been available to Schwann cells in all distal stumps. Endo neurial cell proliferation (predominantly Schwann cell proliferation); levels of expression of c-erbB receptors by Schwann cells, and the de gree to which axons regenerated into the distal stumps all decreased a s the period of prior denervation increased: the longer the time of de nervation, the lower the expression of c-erbBs in Schwann cells, and t he smaller the percentage of bands of Bungner which were re-innervated . (C) 1997 Wiley-Liss, Inc.