TENASCIN-C EXPRESSION DURING WALLERIAN DEGENERATION IN C57BL WLD(S) MICE - POSSIBLE IMPLICATIONS FOR AXONAL REGENERATION/

Schwann cells in the distal stumps of lesioned peripheral nerves stron gly express the extracellular matrix glycoprotein tenascin-C. To gain insights into the relationship between Wallerian degeneration, lesion induced tenascin-C upregulation and regrowth of axons we have investig ated C57BL/Wld(s) (C57BL/Ola) mice, a mutant in which Wallerian degene ration is considerably delayed. Since we found a distinct difference i n the speed of Wallerian degeneration between muscle nerves and cutane ous nerves in 16-week-old C57BL/Wld(s) mice, as opposed to 6-week-old animals in which Wallerian degeneration is delayed in both, we chose t he older animals for closer investigation. Five days post lesion tenas cin-C was upregulated in the muscle branch (quadriceps) but not in the cutaneous branch (saphenous) of the femoral nerve in 16-week-old anim als. In addition myelomonocytic cells displaying endogenous peroxidase activity invaded the muscle branch readily whereas they were absent f rom the cutaneous branch at this time. We could further show that it i s only a subpopulation of axon-Schwann cell units (mainly muscle effer ents) in the muscle branch which undergo Wallerian degeneration and up regulate tenascin-C at normal speed and that the remaining axon-Schwan n cell units (mainly afferents) displayed delayed Wallerian degenerati on and no tenascin-C expression. Regrowing axons could only be found i n the tenascin-C-positive muscle branch where they always grew in asso ciation with axon-Schwann cell units undergoing Wallerian degeneration . These observations indicate a tight relationship between Wallerian d egeneration, upregulation of tenascin-C expression and regrowth of axo ns, suggesting an involvement of tenascin-C in peripheral nerve regene ration.