期刊
EXPERIMENTAL NEUROLOGY
卷 234, 期 1, 页码 62-69出版社
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.expneurol.2011.12.015
关键词
Mice; Diabetes; Neuropathy; Skin innervation; Epidermis; Glyoxalase I; Dorsal root ganglion; Peripheral nerve; Mechanical sensitivity
资金
- Juvenile Diabetes Research Foundation
- NIH [RO1NS43314]
- Kansas IDDRC [P30 NICHD HD 002528]
Diabetic neuropathy is a common complication of diabetes mellitus with over half of all patients developing neuropathy symptoms due to sensory nerve damage. Diabetes-induced hyperglycemia leads to the accelerated production of advanced glycation end products (AGEs) that alter proteins, thereby leading to neuronal dysfunction. The glyoxalase enzyme system, specifically glyoxalase I (GLO1), is responsible for detoxifying precursors of AGEs, such as methylglyoxal and other reactive dicarbonyls. The purpose of our studies was to determine if expression differences of GLO1 may play a role in the development of diabetic sensory neuropathy. BALB/cJ mice naturally express low levels of GLO1, while BALB/cRyJ express approximately 10-fold higher levels on a similar genetic background due to increased copy numbers of GLO1. Five weeks following STZ injection, diabetic BALB/cJ mice developed a 68% increase in mechanical thresholds, characteristic of insensate neuropathy or loss of mechanical sensitivity. This behavior change correlated with a 38% reduction in intraepidermal nerve fiber density (IENFD). Diabetic BALB/cJ mice also had reduced expression of mitochondrial oxidative phosphorylation proteins in Complexes I and V by 83% and 47%, respectively. Conversely, diabetic BALB/cByJ mice did not develop signs of neuropathy, changes in IENFD, or alterations in mitochondrial protein expression. Reduced expression of GLO1 paired with diabetes-induced hyperglycemia may lead to neuronal mitochondrial damage and symptoms of diabetic neuropathy. Therefore, AGEs, the glyoxalase system, and mitochondrial dysfunction may play a role in the development and modulation of diabetic peripheral neuropathy. (C) 2011 Elsevier Inc. All rights reserved.
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