Da. Kirschner et J. Eichberg, RESTRICTED HYPOTONIC SWELLING OF PERIPHERAL-NERVE MYELIN IN STREPTOZOCIN-INDUCED DIABETIC RATS, Journal of neuroscience research, 38(2), 1994, pp. 142-148
Experimental diabetic neuropathy includes the nonenzymatic glycosylati
on (or glycation) of the major proteins of peripheral nerve myelin. We
have used X-ray diffraction to determine whether such glycation affec
ts myelin membrane structure and interactions in peripheral nerves fro
m experimental diabetic rats. Streptozocin at 60 mg/kg was injected in
traperitoneally to induce diabetes; controls were pair-fed and age-mat
ched. Animals were sacrificed periodically from 2 weeks to after 1 yea
r. The dissected sciatic nerves were tied off and incubated overnight
at room temperature in hypotonic saline of defined pH and ionic streng
th or in distilled water. Such treatments have been shown to result in
systematic changes of myelin period, which can be detected using X-ra
y diffraction, and which may indicate alterations in inter-membrane in
teractions owing to changes in composition. We observed no differences
in repeat periods between control and diabetic nerves at pH 4.0 and 7
.4, and ionic strength 0.01, 0.02, 0.06, 0.15, and 0.18; however, we d
id detect a significant difference (P < .02) in their maximum extent o
f swelling in distilled water: control nerves showed a period of 292 A
ngstrom (s.d. 23 Angstrom; n = 12) compared to 272 Angstrom (s.d. 19 A
ngstrom; n = 11) for diabetic nerves. To determine whether this differ
ence in swelling was due to an alteration in the properties of the app
osed, extracellular surfaces of the myelin membranes or to the connect
ive tissue in peripheral nerve, we compared the X-ray patterns from pe
ripheral nerve myelin isolated by sucrose density gradient centrifugat
ion from sciatic nerves of diabetic and control rats. No difference in
the patterns was observed. Since the maximum extent of myelin membran
e swelling in peripheral nerves is limited by the collagen, our result
s suggest that the collagen in the nerves of diabetic rats is less ela
stic or more densely packed than in the controls, most likely due to N
-glycation-mediated cross-linking. (C) 1994 Wiley-Liss, Inc.