Impaired molecular regenerative responses in sensory neurones of diabetic rats: gene expression changes in dorsal root ganglia after sciatic nerve crush.
This study investigated changes in gene expression in lumbar dorsal root ganglia (DRG), contralateral and ipsilateral to a sciatic nerve crush in control and streptozotocin (STZ)-induced diabetic rats. After 10 weeks of diabetes, the left sciatic nerves of all rats were crushed at mid-thigh level, and the rats were maintained for a further 2 weeks. Northern blots, with internal standards, were made from L4 and L5 (pooled) DRG on each side to compare RNA hybrids from ganglia attached to crushed nerves with those attached to intact nerves. The expression of growth-associated proteins, GAP-43 and Talpha1 alpha-tubulin mRNA in DRG, was stimulated (all P < 0.05) by crush injury in control and diabetic rats. Steady-state expression of transcripts for neurofilament (NF) proteins (NF-L, NF-H) and the high-affinity NGF receptor, trkA was decreased by diabetes in the contralateral ganglia to the crush (all P < 0.05). Crush injury further decreased expression of these transcripts in both control and diabetic rats (all P < 0.05). This reduced expression of mRNA coding for both growth-associated proteins, and neurofilament proteins in ganglia of diabetic rats could participate in the reduced competence of the regenerative response to nerve crush.
Mohiuddin
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Department of Pharmacology, Medical Sciences, St. Batholomew's and the London School of Medicine at QMW, Queen Mary and Westfield College, England, U.K.
Tomlinson
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DR
D000818:Animals; D015152:Blotting, Northern; D003921:Diabetes Mellitus, Experimental / Q000503:physiopathology*; D007839:Functional Laterality; D019922:GAP-43 Protein / Q000235:genetics; D005727:Ganglia, Spinal / Q000378:metabolism*; D015870:Gene Expression; D008297:Male; D009409:Nerve Crush; D009416:Nerve Regeneration / Q000235:genetics*; D016900:Neurofilament Proteins / Q000235:genetics; D009475:Neurons, Afferent / Q000502:physiology*; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017208:Rats, Wistar; D012584:Sciatic Nerve / Q000503:physiopathology*; D014404:Tubulin / Q000235:genetics
D019922:GAP-43 Protein; D016900:Neurofilament Proteins; D012333:RNA, Messenger; D014404:Tubulin