Streptozotocin-induced diabetes mellitus causes changes in primary sensoryneuronal cytoskeletal mRNA levels that mimic those caused by axotomy

Dorsal root ganglion (DRG) sensory neurons are particularly vulnerable to d iabetes mellitus. There is evidence that the disease decreases both circula ting and retrogradely transported neurotrophic factors that are essential t o the normal maintenance and function of these cells. A substantive loss of trophic support should cause DRG neurons to respond as though they were ax otomized and, like an axotomy, cause significant changes in cytoskeletal ge ne expression within these cells. Such changes might contribute to the defi cits in sensory neuronal function that characterize diabetic neuropathy. Th e current study used quantitative in situ hybridization to test the hypothe sis that streptozotocin-induced diabetes, like ale axotomy, increases class III beta-tubulin gene expression and decreases neurofilament 68-kDa gene e xpression in lumbar DRG neurons. In animals that had been diabetic for 8 we eks with mean blood glucose levels of 340 mg/dl, lumbar DRG class III beta- tubulin mRNA mean steady-state levels were twofold higher than those in age -matched nondiabetic controls. Moreover, in the same animals, diabetes decr eased lumbar DRG 68-kDa neurofilament mRNA mean steady-state levels by more than half. These data show that diabetes causes changes in primary sensory neuronal cytoskeletal gene expression that mimic those caused by axotomy. Moreover, they support the idea that a loss of neurotrophic support contrib utes to the pathogenesis of diabetic neuropathy. (C) 1998 Academic Press.