Details

Autor(en) / Beteiligte

• SCHMEICHEL, Ann M
• SCHMELZER, James D
• LOW, Phillip A

Titel

Oxidative Injury and Apoptosis of Dorsal Root Ganglion Neurons in Chronic Experimental Diabetic Neuropathy

Ist Teil von

• Diabetes (New York, N.Y.), 2003-01, Vol.52 (1), p.165-171

Ort / Verlag

Alexandria, VA: American Diabetes Association

Erscheinungsjahr

2003

Quelle

EZB-FREE-00999 freely available EZB journals

Beschreibungen/Notizen

• Oxidative Injury and Apoptosis of Dorsal Root Ganglion Neurons in Chronic Experimental Diabetic Neuropathy Ann M. Schmeichel , James D. Schmelzer and Phillip A. Low From the Department of Neurology, Mayo Clinic, Rochester, Minnesota 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. Footnotes Address correspondence and reprint requests to Phillip A. Low, Department of Neurology, Mayo Clinic, 200 First St. SW, Rochester, MN 55905. E-mail: low{at}mayo.edu . Received for publication 25 March 2002 and accepted in revised form 23 September 2002. 8-OHdG, 8-hydroxy-2′-deoxyguanosine; DRG, dorsal root ganglion; EDN, experimental diabetic neuropathy; GSH, reduced glutathione; STZ, streptozotocin; TUNEL, TdT-mediated dUTP-biotin nick end labeling. DIABETES