Expression of axotomy-inducible and apoptosis-related genes in sensory nerves of rats with experimental diabetes.
In diabetes, peripheral nerves suffer deficient neurotrophic support-a situation which resembles axotomy. This raises the question: does inappropriate establishment of an axotomised neuronal phenotype contribute to diabetic neuropathy, and in extremis, does this provoke apoptosis? We hybridized reverse-transcribed RNA, from the dorsal root ganglia (DRG) of 8-week streptozotocin (STZ)-induced diabetic rats, to Affymetrix Rat Genome U34A chips and scanned the array for expression of (a) genes that are upregulated by axotomy, (b) proapoptotic and (c) anti-apoptotic genes. Expression of the axotomy-responsive genes coding for growth-associated protein 43 (GAP-43), galanin, neuropeptide Y (NPY), pre-pro-vasoactive intestinal polypeptide (pre-pro-VIP), neuronal nitric oxide synthase (nNOS), protease nexin 1, heat-shock protein 27 (HSP 27) and myosin light chain kinase II (MLCK II) was unaffected in ganglia from diabetic rats compared to controls; thus, no axotomised phenotype was established. The expression of the majority of proapoptotic genes in the DRG was also unaltered (bax, bad, bid, bok, c-Jun, p38, TNFR1, caspase 3 and NOS2). Similarly there was no change in expression of the majority of antiapoptotic genes (bcl2, bcl-xL, bcl-w, NfkappaB). These alterations in gene expression make it clear that neither axotomy nor apoptotic phenotypes are established in neurones in this model of diabetes.
Burnand
R C
RC
Division of Neuroscience, School of Biological Sciences, University of Manchester, 1.124 Stopford Building, Oxford Road, Manchester M13 9PT, UK.
Price
S A
SA
McElhaney
M
M
Barker
D
D
Tomlinson
D R
DR
D000818:Animals; D017209:Apoptosis / Q000235:genetics*; D019771:Axotomy; D003921:Diabetes Mellitus, Experimental / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology*; D003929:Diabetic Neuropathies / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology*; D020869:Gene Expression Profiling; D009431:Neural Conduction; D009475:Neurons, Afferent / Q000473:pathology / Q000502:physiology*; D051381:Rats