INCREASED VULNERABILITY TO DEMYELINATION IN STREPTOZOTOCIN-DIABETIC RATS

Demyelination is a prominent feature in nerve biopsies of patients wit h diabetic neuropathy. The mechanism is unknown because diabetic roden ts, unlike humans, do not consistently develop segmental demyelination . We examined how diabetes influences toxicant-induced demyelination, remyelination, Schwann cell. nerve growth factor receptor (p75) expres sion, and endoneurial macrophage apolipoprotein E (ape E) synthesis in diabetic rats. Postnatal day 17 (P17) rats were given 110 mg/kg strep tozotocin intraperitoneally and then fed a diet containing metallic te llurium (Te) from P20 to P27 to induce demyelination. Transverse elect ron micrographs and immunostained longitudinal cryosections were prepa red from sciatic nerve during demyelination and remyelination. Diabeti c rats had a mean serum glucose concentration of 490 mg/dl and consume d equivalent doses of peroral Te. The number of demyelinated fibers in electron micrographs was increased significantly by 17% (P <.0011). E ndoneurial density of p75-stained Schwann cells was increased in diabe tic rats in proportion to the increased number of injured internodes. Density of apo E- and ED1-positive macrophages also was significantly increased in diabetes. There was no delay in macrophage myelin clearan ce, and remyelination was not compromised. Increased Schwann cell vuln erability to stress, by increasing the turnover rate of myelinated uni ts, may explain why myelin defects accumulate after long-standing diab etes. (C) 1996 Wiley-Liss, Inc.