Schwann cell nerve growth factor receptor expression during initiation of remyelination.
Initiation of remyelination is a promising therapeutic strategy to treat patients with demyelinating diseases, but specific factors that control remyelination are not clear. We first reported that expression of nerve growth factor receptor (NGFR) was increased during initiation of remyelination (Fan and Gelman, Journal of Neuropathology and Experimental Neurology 49: 312, 1990). In this study, we characterized the timing and cellular localization of NGFR expression in a model of segmental demyelination and remyelination using immunohistochemistry and monoclonal antibody 192-IgG, and compared it to an axonal neuropathy. At the onset of demyelination induced by tellurium (Te) poisoning, NGFR antigenicity was selectively expressed within and around demyelinating internodes in rat sciatic nerve. Dual fluorescence staining with myelin-specific antigen showed that NGFR colocalized with demyelinated internodal units with relative specificity; Schwann cell S-100 protein showed a concomitant down-regulation in injured internodes. Peak expression of NGFR occurred during the transition between demyelination and remyelination (day 8 of Te), then declined exponentially. NGFR expression was most prominent in the cytoplasm of daughter Schwann cells as they established contact with denuded axons, and was sharply repressed as compact myelin began to accumulate. Rare colocalization with neurofilament antigens revealed intraxonal deposits of NGFR in segmental demyelination. In the nerve crush model, Schwann cell NGFR expression was not segmentally distributed and was upregulated for a longer period of time. Our data establish that NGFR expression in the peripheral nervous system is not strictly linked to axon elongation, and that it probably functions during the initiation of myelination.
Fan
X
X
Department of Pathology, University of Texas Medical Branch, Galveston 77550.
Gelman
B B
BB
D000818:Animals; D002450:Cell Communication; D003711:Demyelinating Diseases / Q000139:chemically induced / Q000378:metabolism* / Q000503:physiopathology; D003714:Denervation; D005786:Gene Expression Regulation; D008297:Male; D009186:Myelin Sheath / Q000502:physiology*; D009409:Nerve Crush; D009413:Nerve Fibers, Myelinated / Q000502:physiology / Q000648:ultrastructure; D009414:Nerve Growth Factors / Q000502:physiology*; D009416:Nerve Regeneration / Q000502:physiology*; D051381:Rats; D011956:Receptors, Cell Surface / Q000096:biosynthesis* / Q000235:genetics / Q000502:physiology; D017475:Receptors, Nerve Growth Factor; D012583:Schwann Cells / Q000378:metabolism* / Q000502:physiology; D012584:Sciatic Nerve / Q000502:physiology / Q000648:ultrastructure; D013691:Tellurium / Q000633:toxicity; D015854:Up-Regulation
D009414:Nerve Growth Factors; D011956:Receptors, Cell Surface; D017475:Receptors, Nerve Growth Factor; D013691:Tellurium