REGULATION OF SCHWANN-CELL NUMBERS IN TELLURIUM-INDUCED NEUROPATHY - APOPTOSIS, SUPERNUMERARY CELLS AND INTERNODAL SHORTENING

We have used an experimental model of tellurium(Te)-induced demyelinat ing neuropathy in the rat to study cellular mechanisms involved in reg ulating Schwann cell (SC) numbers during remyelination. Starting at po stnatal day 21, weaned rats were fed a diet containing 1.1% elemental Te. Following 7 days of Te treatment and at several time points of pos t-tellurium treatment (PTe), the animals were processed for ultrastruc tural analysis, SC nuclei quantification and teased fibre preparations . It is well-established that Te induces a transient demyelinating/rem yelinating sequence in sciatic nerves. The loss of the myelin sheath i n this neuropathy produces active proliferation and overproduction of immature SCs. By electron microscopy analysis most mitotic SCs were lo cated along demyelinated segments. Quantitative determination of SC nu clei per transverse section of sciatic nerve revealed a dramatic incre ase of SCs at 2 days PTe relative to control nerves. The number of SC nuclei then decreased progressively during the long-term period of rec overy studied (330 days PTe). In Te-treated rats, SCs undergoing cell death were regularly found within the nerve fibre compartment, especia lly on demyelinated segments. Dying cells exhibited morphological feat ures of apoptosis and appeared enclosed by lamellar processes of adjac ent healthy SCs in extracellular compartments. Both healthy immature S Cs and endoneurial macrophages were involved in the phagocytosis of ap optotic SCs. Particularly during remyelination, supernumerary endoneur ial SCs were observed surrounding myelinated fibres. These cells progr essively became atrophic with a morphological phenotype similar so tha t of ''onion bulb'' cells. On the other hand, teased fibre measurement s revealed a remarkable permanent internodal shortening in remyelinate d fibres from Te-treated sciatic nerves. These results indicate that a portion of redundant immature SCs are susceptible to elimination by a poptosis. However, other distinct biological mechanisms such as the pe rsistence of supernumerary SCs in the endoneurium and the shortening o f internodal lengths are also involved in regulating SC numbers during the remyelination stage.