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Diabetes, Vol 47, Issue 11 1779-1785, Copyright © 1998 by American Diabetes Association

ARTICLES

Effect of nerve growth factor treatment on p75NTR gene expression in lumbar dorsal root ganglia of streptozocin-induced diabetic rats

JD Delcroix, GJ Michael, JV Priestley, DR Tomlinson and P Fernyhough
Department of Pharmacology, St. Bartholomews' and Royal London Hospital School of Medicine and Dentistry, Queen Mary and Westfield College, University of London, UK.

Previous work shows that gene expression for p75NTR in lumbar dorsal root ganglia (DRG) is deficient in streptozocin-induced diabetic rats, while expression of trkA protein is unaffected. This is the first study on the effect of diabetes on immunohistochemical staining and axonal transport of p75NTR in sensory neurons. We also investigated the novel effect of nerve growth factor (NGF) treatment on the levels of mRNA and protein of the NGF receptors, trkA and p75NTR, in normal and diabetic rats. Immunohistochemical staining for p75NTR was significantly reduced in DRG of 12-week streptozocin-induced diabetic rats, confirming the previous work. Anterograde and retrograde axonal transport of p75NTR within the sciatic nerve was similarly decreased in diabetic rats, while levels of transport of trkA were unaffected. Treatment with systemic NGF reversed the diabetes-induced deficit in p75NTR transcripts and protein within the DRG and left expression levels of trkA unchanged. We propose that in sensory neurons of diabetic rats, the ability to capture and retrogradely transport NGF may be impaired because of suboptimal production of p75NTR receptors and that NGF therapy may overcome this deficiency.
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Copyright © 1998 by the American Diabetes Association.