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Neurosci Lett. 2006 Oct 30;407(3):199-204. Epub 2006 Sep 14.

Selective susceptibility of different populations of sympathetic neurons to diabetic neuropathy in vivo is reflected by increased vulnerability to oxidative stress in vitro.

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  • 1Department of Anatomy and Developmental Biology, University College London, London, UK.

Abstract

Diabetes is the major cause of autonomic neuropathy in humans. Sympathetic neurons from the celiac/superior mesenteric ganglia (CG/SMG) develop neuropathic changes in diabetes whereas sympathetic superior cervical ganglion (SCG) neurons do not. Glucose-induced oxidative stress is proposed as a major factor in the development of diabetic neuropathy. The aim of this study was to investigate whether sympathetic neurons that develop neuropathy in diabetes are more susceptible to oxidative stress. Explants of CG/SMG and SCG from control adult rats were cultured in media free of serum and NGF, exposed to menadione for 48 h to induce oxidative stress and assessed for neuronal viability, TUNEL-positive nuclei and tyrosine hydroxylase- (TH)-immunoreactivity. TH-immunoreactivity was also assessed in ganglia from control and 8 week streptozotocin-diabetic rats. Menadione caused a concentration-dependent loss of neuronal viability and increase in TUNEL staining in both ganglia. However, at low concentrations, menadione had a significantly greater effect (p<0.01) on CG/SMG neurons than SCG neurons. At 1 nM, menadione caused a significant increase (p<0.05) in the number of CG/SMG neurons containing intense TH-immunoreactivity without affecting SCG neurons. Similarly, 8 weeks streptozotocin-induced diabetes resulted in a significant increase (p<0.05) in intensely fluorescent TH-containing CG/SMG neurons but not SCG neurons. This is the first demonstration that oxidative stress in vitro causes the same accumulation of TH in CG/SMG neurons as is observed following streptozotocin-induced diabetes in vivo. Furthermore, the selective vulnerability of CG/SMG neurons to diabetes is reflected by increased sensitivity to oxidative stress.

PMID:
16973273
[PubMed - indexed for MEDLINE]
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