Depletion of taurine in experimental diabetic neuropathy: Implications fornerve metabolic, vascular, and functional deficits

Citation
R. Pop-busui et al., Depletion of taurine in experimental diabetic neuropathy: Implications fornerve metabolic, vascular, and functional deficits, EXP NEUROL, 168(2), 2001, pp. 259-272
Citations number
85
Categorie Soggetti
Neurosciences & Behavoir
Journal title
EXPERIMENTAL NEUROLOGY
ISSN journal
00144886 → ACNP
Volume
168
Issue
2
Year of publication
2001
Pages
259 - 272
Database
ISI
SICI code
0014-4886(200104)168:2<259:DOTIED>2.0.ZU;2-F
Abstract
In diabetes, increased oxidative stress, disruption of signal transduction pathways, and endothelial dysfunction have been critically implicated in th e pathogenesis of experimental diabetic neuropathy (EDN). The development o f nerve conduction slowing in diabetes is accompanied by depletion of the p -amino acid taurine, Since taurine functions as an antioxidant, calcium mod ulator, and vasodilator, taurine depletion may provide a pathogenetic link between nerve metabolic, vascular, and functional deficits complicating dia betes, The mechanism(s) of nerve taurine depletion, the localization of cri tical taurine deficits, and its pathophysiological significance in EDN are however unknown. This study explored the pathophysiological effects of sele ctive nerve taurine replacement in streptozotocin-diabetic (STZ-D) rats. A polyclonal human taurine transporter (TT) antibody was also generated in or der to determine potential loci of critical taurine depletion. Two weeks of STZ-D reduced sciatic motor nerve conduction velocity (NCV) by 23% (P < 0, 01), decreased composite nerve blood flow by 38% (P < 0,01), and reduced ne rve taurine content by 29% (P < 0,05). In STZ-D rats, a 1% taurine diet cor rected nerve taurine depletion, prevented motor NCV slowing, and partially attenuated composite nerve blood flow deficits. After 6 weeks of STZ-D, a 1 % taurine diet ameliorated motor NCV slowing and endoneurial nutritive bloo d flow deficits, prevented digital sensory NCV slowing, and reduced ouabain -sensitive nerve (Na,K)-ATPase activity. Immunohistochemical studies locali zed taurine and the TT to the vascular endothelium and Schwann cells of the sciatic nerve. In conclusion, taurine depletion in the vascular endotheliu m and Schwann cells of the sciatic nerve may contribute to the neurovascula r and metabolic deficits in EDN, <(c)> 2001 Academic Press.