Experimental diabetic neuropathy: similar changes of slow axonal transport and axonal size in different animal models.
Analysis of slow axonal transport in sciatic and primary visual systems of BB rats with spontaneous diabetes of 2.5-3.5 months duration revealed a delay in transport of the neurofilament (NF) subunits, tubulin, actin, and the 60, 52, and 30 kDa polypeptides in both systems. The polypeptides examined were not affected uniformly. Rather, the transport of the 60, 52, and 30 kDa polypeptides and the rapidly moving component of tubulin, all constituents of the slow component b (SCb) of axonal transport, appeared to be more severely delayed than the transport of polypeptide constituents of the slow component a (SCa), such as NF and the slow-moving tubulin. Transport was not impaired in diabetic BB rats maintained normoglycemic with optimal doses of insulin. A 52 kDa polypeptide constituent of SCb was identified as neuron-specific enolase, and the 30 and 60 kDa polypeptides are likely to be aldolase and pyruvate kinase; all 3 are glycolytic enzymes. Morphometric analysis revealed that the cross-sectional area of sciatic axons was increased proximally at the level of the motor roots and decreased distally at the level of the tibial nerve. The changes in slow transport and caliber observed in central and peripheral axonal systems of diabetic BB rats are virtually identical to those previously described in rats with streptozotocin-induced diabetes, another model of insulin-dependent diabetes. In both models, the alterations of axonal caliber are likely to be secondary to the impairment of axonal transport.(ABSTRACT TRUNCATED AT 250 WORDS)
Medori
R
R
Division of Neuropathology, Case Western Reserve University, Cleveland, Ohio 44106.
Jenich
H
H
Autilio-Gambetti
L
L
Gambetti
P
P
D000818:Animals; D001369:Axons / Q000378:metabolism* / Q000648:ultrastructure; D001692:Biological Transport; D003929:Diabetic Neuropathies / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008715:Methionine / Q000378:metabolism; D010455:Peptides / Q000302:isolation & purification; D051381:Rats; D011913:Rats, Inbred BB; D012584:Sciatic Nerve / Q000378:metabolism
D010455:Peptides; D008715:Methionine