Deficient Axonal Transport of Substance P in Streptozocin-Induced Diabetic Rats: Effects of Sorbinil and Insulin

Abstract

This study measured the accumulation of substance P-like immunoreactivity (SPLI) proximal and distal to 12-h constricting ligatures applied to rat sciatic nerves. There were three separate experiments, and the baseline for each consisted of control and age-matched rats with 3 wk of untreated streptozocin-induced diabetes. We compared the effects of twice-daily insulin treatment, daily sorbinil (25 mg.kg-1.day-1 p.o.), and a combination of both treatments. In untreated diabetic rats the anterograde accumulation of SPLI was reduced by 30-40%. This deficit was unaffected by sorbinil alone but was attenuated by insulin and prevented completely by insulin and sorbinil combined. There were also indications that diabetes caused reductions in retrograde accumulation of SPLI and its content in unconstricted nerve and the L4 dorsal root ganglion. The fraction of SPLI undergoing net anterograde or retrograde movement and the velocities of accumulation were unaffected by diabetes or the treatment regimens. These findings indicate a reduction in the amount of substance P moved by axonal transport in diabetic rats that is related partly to aldose reductase activity and partly to some other insulin-correctable consequence of experimental diabetes.

Progressive and selective changes in neurotrophic factor expression and substance p axonal transport induced by perinatal diabetes: Protective action of antioxidant treatment

“…In addition to the normalization of embryonic growth, insulin supplementation to the diabetic mothers prevented the alterations of BDNF, NGF, p75, and IGF-I mRNA and IGF-I protein content in embryos and newborn rats. As already reported in the literature (Tomlison et al, 1988;Di Giulio et al, 1995), SP transport was also normalized by insulin treatment (data not shown).…”

“…Peripheral nerve deficits are characterized by reduced nerve conduction (Norido et al, 1984), progressive axonal atrophy accompanied by reduced neurofilament trasport (Vitadello et al, 1985;Medori et al, 1988), and reduction in anterograde axonal transport (Vitadello et al, 1983;Tomlison et al, 1984). The accumulation of sensory axon substance P at a ligature placed along the sciatic nerve is reduced in diabetic rats (Tomlison et al, 1988;Di Giulio et al, 1995). In more chronic diabetes, the nerve content of substance P is also reduced (Robinson et al, 1987).…”

Human Recombinant Nerve Growth Factor Replaces Deficient Neurotrophic Support in the Diabetic Rat

“…Thus, there is reduced retrograde axonal transport of exogenous NGF (Jakobsen et al, 1981;Schmidt et al, 1986) and reduced levels of endogenous NGF-like immunoreactivity (NGF-LI) in several tissues (Hellweg and Hartung, 1990). Two of the well-established gene targets for NGF-those coding for preprotachykinin A (the substance P precursor) and calcitonin gene-related peptide (CGRP) (Lindsay and Harmar, 1989;)-exhibit reduced expression in the sciatic nerve of diabetic rats (Robinson et al, 1987;Tomlinson et al, 1988;Diemel et al, 1992), and this may be secondary to an NGF deficit. In normal rats injection of radiolabelled NGF into the forepaw results in its carriage to cervical sensory ganglia by retrograde axonal transport (Stoeckel et al, 1975); in the hindlimb, sensory fibres of the sciatic nerve capture labelled NGF injected into the gastrocnemius muscle (Koliatsos et al, 1993); and NGF is produced in adult rat skin (Goedert et al, 1986).…”

Essential fatty acid treatment ? effects on nerve conduction, polyol pathway and axonal transport in streptozotocin diabetic rats

“…Slow anterograde axonal transport of 6-phosphofructokinase activity is deficient in diabetic rats, this deficit is prevented by intensive insulin treatment [9], but is unaffected by treatment with either of two structurally-unrelated aldose reductase inhibitors [9,10]. Fast anterograde axonal transport of substance P is also deficient in rats with streptozotocininduced diabetes mellitus of either 3 weeks' [11] or 9 months' [12] duration. In both cases aldose reductase inhibition attenuated, but did not prevent the deficit, however the deficit was absent in diabetic rats treated with both insulin and an aldose reductase inhibitor [11].…”