Presence of growth inhibitors in fish optic nerve myelin: Postinjury changes

Abstract

This study shows that the fish optic nerve, which is able to regenerate after injury, contains myelin-associated growth inhibitors similar to the growth inhibitors present in mammalian central nervous system (CNS) myelin. The ability of nerves to regenerate was previously correlated with the ability of sections from these nerves to support neuronal attachment and axonal growth in vitro. Thus neuroblastoma cells or embryonic neurons became attached to and grew axons on sections of rat sciatic nerve or fish optic nerve, which are spontaneously regenerating systems, but not on sections of rat optic nerve, a nonregenerating system. Failure of the latter to support axonal growth has been attributed, at least in part, to growth inhibitors. Recently it was shown that adult neurons, which differ in their growth requirement from embryonic neurons, are unable to extend neurites on sections of normal sciatic nerve but are able to extend neurites on sections of sciatic nerve that was injured prior to its excision. We found a similar situation in the fish optic nerve, i.e., that the nerve is normally not permissive to growth of adult retinal axons but becomes growth permissive after injury. The nonpermissiveness of the normal fish optic nerve was found to correlate with the presence of myelin-associated growth-inhibitory molecules. This inhibitory activity of fish myelin was neutralized by IN-1 antibodies, known to neutralize rat myelin growth inhibitors. The results thus demonstrate that fish optic nerve myelin contains inhibitors apparently similar or even identical to those of rat, but possibly present in lower amounts than in the rat. Results are discussed with respect to the possibility that fish optic nerve, like the rat sciatic nerve and unlike the rat optic nerve, undergoes certain changes after injury that support regeneration of adult neurons. Such changes might include elimination or neutralization of growth inhibitors.

Myelin debris clearance during Wallerian degeneration in the goldfish visual system

“…This observation would seem to support the contention that goldfish myelin is not inhibitory to axonal outgrowth (Bastmeyer et al, 1991(Bastmeyer et al, , 1993Strobel and Stuermer, 1994;Wanner et al, 1995;Ankerhold et al, 1998). However, it must also be noted that at later postoperative times, axons appear to be excluded from astrocytic domains in the nerve which contain persistent myelin debris, an observation which suggests that at least this population of debris particles is inhibitory (Sivron et al, 1994;Sivron and Schwartz, 1994a,b). Clearly, these conflicting observations cannot be resolved with the present data and will require further investigation.…”

Repellent Guidance of Regenerating Optic Axons by Chondroitin Sulfate Glycosaminoglycans in Zebrafish

“…In vitro evidence suggests that the myelin inhibitor Nogo-1 (Chen et al, 2000) is absent Wanner et al, 1995) or expressed at lower levels (Sivron et al, 1994) in the regenerating CNS of fish and amphibians. Tenascin-R, another oligodendrocyte-derived inhibitor of axon growth (Pesheva et al, 1989), persists after optic nerve crush in mice (T. but disappears from the injured nerve of salamanders concomitantly with regeneration of optic fibers (Becker et al, 1999).…”

Tenascin‐R and axon growth‐promoting molecules are up‐regulated in the regenerating visual pathway of the lizard (Gallotia galloti)

“…Several putative neurite growth inhibitory proteins and their receptors have been studied in the CNS of fish and amphibians (Bastmeyer et al, 1991;Sivron et al, 1994;Lang et al, 1995;Wanner et al, 1995;Becker et al, 1999Becker et al, , 2002Becker et al, , 2003Becker et al, , 2004Klinger et al, 2004a,b;Pesheva et al, 2006). However, the causal relationship between the expression of neurite growth inhibitors and regenerative capacity in the lower vertebrate CNS remains controversial, and the question whether regeneration of RGC axons in lower vertebrates is generally facilitated by down-regulation or clearance of inhibitory proteins is unresolved.…”

“…However, the causal relationship between the expression of neurite growth inhibitors and regenerative capacity in the lower vertebrate CNS remains controversial, and the question whether regeneration of RGC axons in lower vertebrates is generally facilitated by down-regulation or clearance of inhibitory proteins is unresolved. Downregulation of proteins known to inhibit axon growth in mammals has been described in the fish (Sivron et al, 1994;Becker et al, 2004) and amphibian (Becker et al, 1999) visual system following optic nerve injury. Other studies (Bastmeyer et al, 1991;Wanner et al, 1995) have failed to detect inhibitory activity in CNS myelin and oligodendrocytes of fish.…”