Experimental Diabetic Neuropathy: Effect of Ganglioside Treatment on Axonal Transport of Cytoskeletal Proteins

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.

The effects of Ginkgo biloba extract (GBe) on axonal transport microvasculature and morphology of sciatic nerve in streptozotocin-induced diabetic rats

“…The relationship between Vmean of slow axonal transport and mean diameter of axons in the sciatic nerves in untreated diabetic (/"), GBe-treated diabetic ([2]), and control (O) rats combined (5 rats for each), rs = Spearman's rank correlation coefficient.…”

Stimulation of adult neural stem cells with a novel glycolipid biosurfactant

“…I n vivo treatment with gangliosides has proven effective in attenuating ischemic injury in rats [32] and protecting various cell populations in several model systems of neuronal injury [33]. Additionally, intraperitoneal administration of GSL globotetraosylceramide has been shown to exhibit marked anti-depressive activity on the forced swimming test in mouse [34].…”

Distribution of systemically administered ampicillin, benzylpenicillin, and flucloxacillin in excisional wounds in diabetic and normal rats and effects of local topical vasodilator treatment

“…For the present study, it was important that the rat diabetic model chosen should reflect the changes in skin blood flow and peripheral neuropathy which contribute to the delayed wound healing responses in diabetic patients (1,2,15,26,30,32,34,43). Evidence in the literature points to the suitability of the STZ-treated rat model of diabetes as an experimental model of the human condition also incorporating some of the secondary clinical complications seen in diabetic patients (4,11,18,24,25,27,33,38,47).…”

“…Diabetics are prone to peripheral vascular disease and peripheral neuropathy, particularly in the lower extremities, which result in loss of sensation and reduced ability to detect injury or developing ulcers. Reduced skin blood flow in the lower extremities in diabetics has been attributed to defects in the function of sensory nerve fibers and subsequent control of the microvasculature compared with normal subjects or controls in both diabetic patients and streptozotocin (STZ)treated rats (4,11,18,24,25,27,38,47). Studies examining the effect of various endothelium-dependent and -independent vasodilators have shown that although endothelial function is impaired in diabetes, microvascular smooth muscle responds to normal stimuli (45).…”