Streptozotocin-induced diabetes mellitus causes changes in primary sensory neuronal cytoskeletal mRNA levels that mimic those caused by axotomy.
Dorsal root ganglion (DRG) sensory neurons are particularly vulnerable to diabetes mellitus. There is evidence that the disease decreases both circulating and retrogradely transported neurotrophic factors that are essential to the normal maintenance and function of these cells. A substantive loss of trophic support should cause DRG neurons to respond as though they were axotomized and, like an axotomy, cause significant changes in cytoskeletal gene expression within these cells. Such changes might contribute to the deficits in sensory neuronal function that characterize diabetic neuropathy. The current study used quantitative in situ hybridization to test the hypothesis that streptozotocin-induced diabetes, like an axotomy, increases class III beta-tubulin gene expression and decreases neurofilament 68-kDa gene expression in lumbar DRG neurons. In animals that had been diabetic for 8 weeks 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 decreased 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 contributes to the pathogenesis of diabetic neuropathy.
Liuzzi
F J
FJ
Department of Pathology, Eastern Virginia Medical School, Norfolk, Virginia, 23501, USA.
Bufton
S M
SM
Vinik
A I
AI
D000818:Animals; D019771:Axotomy; D003599:Cytoskeleton / Q000737:chemistry*; D003921:Diabetes Mellitus, Experimental / Q000235:genetics / Q000503:physiopathology*; D005260:Female; D005727:Ganglia, Spinal / Q000166:cytology; D015870:Gene Expression / Q000502:physiology; D017403:In Situ Hybridization; D009410:Nerve Degeneration / Q000503:physiopathology*; D009419:Nerve Tissue Proteins / Q000235:genetics; D016900:Neurofilament Proteins / Q000235:genetics; D009475:Neurons, Afferent / Q000737:chemistry / Q000473:pathology*; D012333:RNA, Messenger / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014404:Tubulin / Q000235:genetics
D009419:Nerve Tissue Proteins; D016900:Neurofilament Proteins; D012333:RNA, Messenger; D014404:Tubulin; C066858:neurofilament protein NF 68