ABSTRACT
Abnormalities in axonal transport of proteins are thought to play an important role in the pathogenesis of diabetic neuropathy. Gangliosides exert a positive action on numerous alterations in biochemistry and physiology of diabetic nerves. This study was undertaken to assess the effects of exogenous gangliosides on the axonal transport of structural proteins such as actin and tubulin in the sensory fibers of short-term (9-wk) and long-term (6-mo) diabetic rats. Adult Sprague-Dawley rats were made diabetic with a single injection of 70 mg/kg streptozocin i.p. Subgroups were injected daily with either highly purified ganglioside mixture (10 mg/kg i.p.) or saline for 1 mo, beginning either 2 or 17 wk after streptozocin injection. Age-matched rats were used as controls. Axonal transport was studied by the pulse-labeling technique. Three weeks after labeling, sciatic nerves were dissected out and processed for sodium dodecyl sulfate-polyacrylamide gel electrophoresis and fluorography. In diabetic rats of both experimental designs, the transport rate of tubulin and actin was decreased by approximately 30% compared with control rats. Ganglioside treatment counteracted such alterations in both 9-wk and 6-mo diabetic rats. These data suggest a pharmacological effect that could be correlated with molecular interactions between integral membrane glycolipids and cytoskeletal elements.
Subject(s)
Axonal Transport/drug effects , Cytoskeletal Proteins/metabolism , Diabetes Mellitus, Experimental/physiopathology , Diabetic Neuropathies/physiopathology , Ganglia, Spinal/physiopathology , Gangliosides/pharmacology , Neurofilament Proteins/metabolism , Sciatic Nerve/physiopathology , Actins/metabolism , Animals , Blood Glucose/metabolism , Electrophoresis, Polyacrylamide Gel , Ganglia, Spinal/drug effects , Ganglia, Spinal/physiology , Glycated Hemoglobin/analysis , Male , Neurofilament Proteins/isolation & purification , Rats , Rats, Inbred Strains , Reference Values , Sciatic Nerve/drug effects , Sciatic Nerve/physiology , Tubulin/metabolismABSTRACT
Brainstem acoustic evoked potentials (BAEPs) were studied in streptozotocin (STZ)-diabetic rats and age-matched controls at 3 and 5 months from induction of the pathology. The diabetic status of the animals was kept uncontrolled throughout the study. Body weight and glycosylated hemoglobin were markedly altered in the diabetic animals (-42%, and +120% of control values, respectively). Neurophysiological results showed an increase in the latency of the major components of BAEPs; this increase was clearly time-dependent for the peripheral component (peak I). The central component (peak IV) was also significantly delayed. However, no significant impairment of the central conduction time was demonstrated by examining the interpeak I-IV latency. In conclusion, BAEPs prove to be a useful non-invasive neurophysiological technique that may help unravel both the relative involvement of the peripheral and central nervous systems in the course of diabetes mellitus, and the evolution of diabetic neuropathy.
