Increased vulnerability to demyelination in streptozotocin diabetic rats.
Demyelination is a prominent feature in nerve biopsies of patients with diabetic neuropathy. The mechanism is unknown because diabetic rodents, unlike humans, do not consistently develop segmental demyelination. We examined how diabetes influences toxicant-induced demyelination, remyelination, Schwann cell nerve growth factor receptor (p75) expression, and endoneurial macrophage apolipoprotein E (apo E) synthesis in diabetic rats. Postnatal day 17 (P17) rats were given 110 mg/kg streptozotocin intraperitoneally and then fed a diet containing metallic tellurium (Te) from P20 to P27 to induce demyelination. Transverse electron micrographs and immunostained longitudinal cryosections were prepared from sciatic nerve during demyelination and remyelination. Diabetic rats had a mean serum glucose concentration of 490 mg/dl and consumed equivalent doses of peroral Te. The number of demyelinated fibers in electron micrographs was increased significantly by 17% (P < .0011). Endoneurial density of p75-stained Schwann cells was increased in diabetic 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 clearance. and remyelination was not compromised. Increased Schwann cell vulnerability to stress, by increasing the turnover rate of myelinated units, may explain why myelin defects accumulate after long-standing diabetes.
Jaffey
P B
PB
Department of Pathology, University of Texas Medical Branch, Galveston 77550, USA.
Gelman
B B
BB
D000818:Animals; D001057:Apolipoproteins E / Q000096:biosynthesis; D003711:Demyelinating Diseases / Q000139:chemically induced / Q000473:pathology / Q000503:physiopathology*; D003921:Diabetes Mellitus, Experimental / Q000150:complications / Q000473:pathology / Q000503:physiopathology*; D003929:Diabetic Neuropathies / Q000209:etiology / Q000473:pathology / Q000503:physiopathology*; D005260:Female; D008264:Macrophages / Q000378:metabolism; D008297:Male; D008657:Metabolic Clearance Rate; D009185:Myelin Proteins / Q000378:metabolism; D009416:Nerve Regeneration / Q000502:physiology; D051381:Rats; D020800:Receptor, Nerve Growth Factor; D017475:Receptors, Nerve Growth Factor / Q000502:physiology*; D012583:Schwann Cells / Q000187:drug effects*; D013691:Tellurium / Q000506:poisoning*; D015854:Up-Regulation
D001057:Apolipoproteins E; D009185:Myelin Proteins; D020800:Receptor, Nerve Growth Factor; D017475:Receptors, Nerve Growth Factor; D013691:Tellurium