Neuroelectrophysiological abnormalities are related to metabolic and advanced non-enzymatic glycation changes in prospectively evaluated diabetic Sprague-Dawley rats

In order to sequentially explore central (CNS) and peripheral (PNS) nervous system abnormalities in experimental diabetes mellitus, neuroelectrophysiological and nervous protein biochemical changes were investigated in streptozotocin diabetic Sprague-Dawley rats after 1.5, 3, 6 and 12 months from induction of diabetes. Visual (VEP), brainstem-auditory (BAEP) and somatosensory (SEP) evoked potentials were evaluated in control and diabetic rats. Advanced glycation end-product (AGE) levels were measured by spectrofluorimetry in protein extracts from central and peripheral nervous tissue samples. Mean VEP (P1 wave) and BAEP (waves I, II and III) latencies were increased whereas SEP (Tarsus-L6, L6-Cortex and T6-Cortex) conduction/propagation velocities were reduced in diabetic rats at all times (p < 0.05 to p < 0.0001), the alterations being already present after 1.5 months from diabetes induction. Similarly, AGE levels in diabetic rat protein extracts were higher than in control animals, the differences becoming statistically significant with the progression of the disease. When metabolic, neuroelectrophysiological and biochemical alterations were evaluated with time in diabetic rats, a rapid initial change was observed, and followed, in the case of the metabolic control, by steadily abnormal values and as well as, in the case of the electrophysiological and biochemical values, by a continuous slow worsening. Finally, a statistically significant association was found between electrophysiological and biochemical parameters. Thus CNS, but more so PNS, neuroelectrophysiological abnormalities and enhanced nervous protein AGE levels appear relatively early after diabetes induction and, in the presence of an altered metabolic status, are correlated and worsen over time.