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Oxidative stress in the pathogenesis of experimental diabetic neuropathy
Author(s) -
Low P. A.,
Schmeichel A.,
Schmelzer J. D.,
Kishi M.
Publication year - 2003
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.85.s2.14_2.x
Subject(s) - oxidative stress , medicine , tunel assay , diabetes mellitus , pathogenesis , peripheral neuropathy , apoptosis , diabetic neuropathy , endocrinology , efferent , pathology , chemistry , immunohistochemistry , afferent , biochemistry
We evaluated the effects of chronic hyperglycemia on L5 DRG neurons. Experimental diabetic neuropathy (EDN) was induced by streptozotocin. We studied peripheral nerve after 1, 3, 12 months of diabetes. A conduction deficit was present from the first month and persisted over 12 months, affecting mainly sensory fibers. 8‐Hydroxy‐deoxyguanosine labeling was significantly increased at all time points in DRG neurons, indicating oxidative injury. Caspase‐3 labeling was 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 percent of neurons undergoing apoptosis (TUNEL staining) at 1 month (8%), 3 months (7%) and 12 months (11%). Morphometry of DRG showed a selective loss (42%) of the largest neurons. These findings support the concept that oxidative stress leads to oxidative injury of DRG neurons, with mitochondrium as a specific target, leading to apoptosis and a predominantly sensory neuropathy.