Identification of changes in gene expression in dorsal root ganglia in diabetic neuropathy: correlation with functional deficits.

摘要

This study aimed to correlate the onset of functional deficits in diabetic neuropathy with changes in gene expression in rat dorsal root ganglia (DRG). After 1, 4, or 8 weeks of streptozotocin-induced diabetes, sensory and motor nerve conduction velocities (NCV) were measured as an indicator of neuropathy and changes in gene expression were measured using Affymetrix oligonucleotide microarrays. No significant changes in NCV were found after 1 week of diabetes, but after 4 and 8 weeks, there was a significant reduction in both sensory and motor NCV. Global gene expression changes in diabetic rat DRG were evident from principal component analysis of microarray data after 1, 4, and 8 weeks. Expression changes in individual genes were relatively small in line with a gradual degenerative neuropathy indirectly resulting from diabetes. Sets of differentially expressed genes have been identified and quantitative reverse transcriptase-polymerase chain reaction has been used to confirm the microarray data for several genes. Gene ontology overrepresentation analysis was performed on the microarray data to identify biologic processes altered in diabetic DRG. The genes identified in this study may be responsible for causing the functional deficits and suggest pathways/processes that require further investigation as possible targets for therapeutic intervention.