Oxidative injury and apoptosis of dorsal root ganglion neurons in chronic experimental diabetic neuropathy.

Abstract

We evaluated the effects of chronic hyperglycemia on L5 dorsal root ganglion (DRG) neurons using immunohistochemical and electrophysiologic techniques for evidence of oxidative injury. Experimental diabetic neuropathy was induced by streptozotocin. To evaluate the pathogenesis of the neuropathy, we studied peripheral nerve after 1, 3, and 12 months of diabetes. Electrophysiologic abnormalities were present from the first month and persisted over 12 months. 8-Hydroxy-2'-deoxyguanosine labeling was significantly increased at all time points in DRG neurons, indicating oxidative injury. Caspase-3 labeling was significantly increased at all three time points, indicating commitment to the efferent limb of the apoptotic pathway. Apoptosis was confirmed by a significant increase in the percentage of neurons undergoing apoptosis at 1 month (8%), 3 months (7%), and 12 months (11%). These findings support the concept that oxidative stress leads to oxidative injury of DRG neurons, with mitochondrium as a specific target, leading to impaired mitochondrial function and apoptosis, manifested clinically as a predominantly sensory neuropathy.

• Authors: Ann M Schmeichel, James D Schmelzer, Phillip A Low
• Journal: Diabetes (Diabetes) Vol. 52 Issue 1 Pg. 165-71 (Jan 2003) ISSN: 0012-1797 [Print] United States
• PMID: 12502508 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• 8-Hydroxy-2'-Deoxyguanosine
• Casp3 protein, rat
• Caspase 3
• Caspases
• Deoxyguanosine

Topics

• 8-Hydroxy-2'-Deoxyguanosine
• Animals
• Apoptosis (physiology)
• Caspase 3
• Caspases (metabolism)
• Chronic Disease
• Deoxyguanosine (analogs & derivatives, metabolism)
• Diabetic Neuropathies (enzymology, pathology, physiopathology)
• Electrophysiology
• Ganglia, Spinal (enzymology, pathology, physiopathology)
• Histocytochemistry
• In Situ Nick-End Labeling
• Male
• Neurons (pathology, physiology)
• Oxidative Stress (physiology)
• Rats
• Rats, Sprague-Dawley