CHRONICALLY DENERVATED RAT SCHWANN-CELLS RESPOND TO GGF IN-VITRO

C-erbB receptor/neuregulin signalling plays a significant role in Schw ann cell function. In vivo, Schwann cells up-regulate expression of c- erbB receptors in the first month after injury, but receptor expressio n is down-regulated with time to levels that are not detectable immuno histochemically. The inability of chronically denervated Schwann cells to respond adequately to signals derived from regenerating axons may be one reason why delayed repair of an injured peripheral nerve freque ntly fails. We have examined the effects of GGF on denervated Schwann cells in vitro. A modified delayed dissociation technique was used to obtain adult rat Schwann cells from the distal stumps of transected sc iatic nerves which had been acutely (7 days) or chronically (2-6 month ) denervated. We found that in vitro denervated Schwann cells invariab ly expressed p75(NTR) and c-erbB receptors. There was a progressive de crease in total cell yield and the percentage of cells with Schwann ce ll phenotype (p75(NTR) and/S-100 or/laminin or /GFAP or/c-erbB positiv e); proliferation rate; migratory potential; and expression of the cel l adhesion molecules N-CAM and N-cadherin, with increasing time of den ervation. Addition of GGF2 had a significant stimulatory effect upon S chwann cell proliferation and migration, and an increased proportion o f Schwann cells expressed N-CAM and N-cadherin, suggesting that these responses were mediated via GGF/c-erbB signalling. Our results support the view that it may be possible to manipulate chronically denervated Schwann cells so that they become more responsive to signals derived from regrowing axons. (C) 1998 Wiley-Liss, Inc.