Chronically denervated rat schwann cells respond to GGF in vitro

• Published in: Glia Vol. 24; no. 3; pp. 290 - 303
• Main Authors: Li, H., Wigley, C., Hall, S.M.
• Format: Journal Article
• Language: English
• Published: New York John Wiley & Sons, Inc 01.11.1998; Wiley-Liss
• Subjects: Animals; Axons - physiology; Biological and medical sciences; c-erbB receptors; Cadherins - metabolism; cell cultures; Cell Division - physiology; Coculture Techniques; Denervation; Female; Fundamental and applied biological sciences. Psychology; Glia Maturation Factor; Growth Inhibitors - pharmacology; Immunohistochemistry; Isolated neuron and nerve. Neuroglia; Nerve Growth Factors - pharmacology; Nerve Regeneration - physiology; nerve repair; Nerve Tissue Proteins - pharmacology; Neural Cell Adhesion Molecules - metabolism; neuregulin; Phenotype; Proto-Oncogene Proteins - metabolism; Rats; Rats, Wistar; Receptor, Epidermal Growth Factor - metabolism; Receptor, ErbB-2 - metabolism; Receptor, ErbB-3; Receptor, Nerve Growth Factor; Receptors, Nerve Growth Factor - metabolism; Recombinant Proteins - pharmacology; Schwann Cells - cytology; Schwann Cells - physiology; Schwann Cells - ultrastructure; Sciatic Nerve - cytology; Sciatic Nerve - physiology; Sciatic Nerve - ultrastructure; Vertebrates: nervous system and sense organs; Vertebrata; Mammalia; Rat; Schwann cell; Neuroglia; Rodentia; Neuregulin; Lesion; In vitro; Sciatic nerve; Denervation; Growth factor
• ISSN: 0894-1491; 1098-1136
• DOI: 10.1002/(SICI)1098-1136(199811)24:3<290::AID-GLIA3>3.0.CO;2-6

C‐erbB receptor/neuregulin signalling plays a significant role in Schwann cell function. In vivo, Schwann cells up‐regulate expression of c‐erbB receptors in the first month after injury, but receptor expression is down‐regulated with time to levels that are not detectable immunohistochemically. 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 frequently 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 sciatic nerves which had been acutely (7 days) or chronically (2–6 month) denervated. We found that in vitro denervated Schwann cells invariably expressed p75NTR and c‐erbB receptors. There was a progressive decrease in total cell yield and the percentage of cells with Schwann cell phenotype (p75NTR and/S‐100 or/laminin or /GFAP or/c‐erbB positive); proliferation rate; migratory potential; and expression of the cell adhesion molecules N‐CAM and N‐cadherin, with increasing time of denervation. Addition of GGF2 had a significant stimulatory effect upon Schwann cell proliferation and migration, and an increased proportion of 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. GLIA 24:290–303, 1998. © 1998 Wiley‐Liss, Inc.