Does CNS Myelin Inhibit Axon Regeneration?

Abstract

Membrane proteins on oligodendrocytes and CNS myelin (NI35/250) have been shown to block axon out-growth in culture, and this is thought to be one of the major reasons for severely limited regeneration of severed axons in the CNS of higher vertebrates. In a recent study, adult dorsal root ganglion (DRG) neurons, which are sensitive to these inhibitory proteins, regenerated successfully after transplantation into two white matter tracts of the rat brain without any intervention to suppress the inhibitory activity of CNS myelin. The results and implications of these two studies are considered.

Keywords: Astrocytes; Axon regeneration; Extracellular matrix; Gliosis; Myelin; NI35/250; Oligodendrocytes; Proteoglycan; Spinal cord injury.

Fig. 1.

Regenerated corticospinal axons in an adult rat spinal cord 2 weeks after lesion and infusion of a recombinant partially humanized IN-1 Fab’ antibody fragment. Sagittal section, rostral to the right, lesion is characterized by cavern.

Fig. 2.

Regenerating adult dorsal root ganglion (DRG) axons in adult rat corpus callosum. A, Confocal montage of a portion of an intracallosal adult DRG microtransplant scanned through two adjacent 60-mm horizontal sections. CGRP positive donor adult axons (red) exited the graft and extended within host white matter to cross the midline (M, arrowhead) to enter the contralateral hemisphere. Satellite cells (p75 positive) (green) were associated with donor neuron cell bodies (e.g., arrow), but not with axons. Asterisk indicates a calcitonin gene-related peptide- (CGRP) positive donor neuron near the transplant interface with host white matter. Survival at 4 days; scale bar 100 mM. B, High power confocal image through 17 mm of tangentially sectioned tissue showing a CGRP positive (red) adult donor axon with a streamlined growth cone extending through the myelin rich (CNS myelin specific Mab 328; green) adult host callosum, 2.5 mm from the graft. Inset, low power image of Mab 328 immunohistochemistry shows typical myelin rings when white matter is cut in cross section. Survival, 4 days; scale bar 10 mm. C, Confocal image of donor adult CGRP positive axon terminal within host cortical grey matter. Survival 6 days, scale bar 50 mm. Reprinted with permission from Nature (Davies SJ, Fitch MT, Memberg SP, Hall AK, Raisman G, Silver J. Regeneration of adult axons in white matter tracts of the central nervous system. Nature 1997;390:680–683) Copyright 1997 Macmillan Magazines Limited.