Schwann cell changes induced as early as one week after galactose intoxication.
In galactose neuropathy, aldose reductase inhibitor (ARI)-preventable Schwann cell injury has been reported in studies in which galactose feeding continued over a period of months. Given the link between these morphologic changes and polyol pathway flux, polyol accumulation after just days of galactose feeding points to the possibility that structural changes occur much earlier than previously reported. The aim of this study was to examine rat sciatic nerve after 7 days of galactose feeding for evidence of myelinated fiber injury and establish whether it is related to polyol accumulation. Compared to control or ARI-treated galactose-fed rats, nerves from untreated galactose-fed rats had increased water (P < 0.05) ad dulcitol (P < 0.008) content and decreased amounts of myo-inositol (P < 0.01). Electron microscopy revealed reactive Schwann cell changes in myelinated fibers characterized by increased cytoplasmic volume, and the occurrence of lipid droplets pi granules of Reich and enlarged mitochondria. Dystrophic accumulation of intermediate filaments was also observed in the inner glial loop. Degenerative changes included periaxonal swelling, enlarged mitochondria without recognizable cristae, lysis of Schwann cell cytoplasm and demyelination. Reactive (P < 0.05) and degenerative (P < 0.01) changes as well as the number of redundant basal lamina profiles (P < 0.05) were significantly more frequent in untreated galactose-fed rats compared to controls. ARI treatment attenuated these changes. Consistent with the initial stages of onion-bulb formation, profiles with imbricate Schwann cells were also seen only in untreated galactose-fed rats. The findings suggest that short-term increases in polyol pathway activity can have deleterious effects Schwann cells of myelinated fibers.
Mizisin
A P
AP
Veterans Administration Medical Center, San Diego, La Jolla, CA, USA. amizisin@ucsd.edu
Powell
H C
HC
D000284:Administration, Oral; D000449:Aldehyde Reductase / Q000037:antagonists & inhibitors; D000818:Animals; D003929:Diabetic Neuropathies / Q000139:chemically induced / Q000473:pathology; D004334:Drug Administration Schedule; D005260:Female; D005690:Galactose / Q000633:toxicity*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012583:Schwann Cells / Q000187:drug effects* / Q000473:pathology* / Q000648:ultrastructure; D012584:Sciatic Nerve / Q000187:drug effects / Q000473:pathology / Q000648:ultrastructure; D013997:Time Factors
D000449:Aldehyde Reductase; D005690:Galactose