The impact of diabetes on CNS. Role of bioenergetic defects

To address the problem of the pathogenesis in diabetic neuropathy, rats were made diabetic by streptozotocin administration, and discrete brain regions, such as cortex, cerebellum, brainstem, thalamus, and hypothalamus, were sampled for assay of activities of electron transport chain complexes I-IV at 1 and 3 mo after induction of diabetes. Significant decrease was seen in activities of dinitrophenylhydrazine DNPH-coenzyme Q reductase (complex I), coenzyme Q cytochrome-c reductase (complex III), and cytochrome-c oxidase (complex IV) from discrete brain regions with more pronounced changes in complex I. The decline in the complex I, III, and IV activity was more severe in the 3-mo group. Succinate dehydrogenase (SDH) coenzyme Q reductase (complex II), which is an enzyme shared by tricarboxylic acid (TCA) cycle and electron transport chain, showed a significant increase under the same set of conditions. These results suggest that the bioenergetic impairment has an important role in the pathophysiology of diabetes.