EFFECT OF NERVE GROWTH-FACTOR TREATMENT ON P75(NTR) GENE-EXPRESSION IN LUMBAR DORSAL-ROOT GANGLIA OF STREPTOZOCIN-INDUCED DIABETIC RATS

Previous work shows that gene expression for p75(NTR) in lumbar dorsal root ganglia (DRG) is deficient in streptozocin-induced diabetic rats , while expression of trkA protein is unaffected. This is the first st udy on the effect of diabetes on immunohistochemical staining and axon al transport of p75(NTR) in sensory neurons. We also investigated the novel effect of nerve growth factor (NGF) treatment on the levels of m RNA and protein of the NGF receptors, trkA and p75(NTR), in normal and diabetic rats. Immunohistochemical staining for p75(NTR) was signific antly reduced in DRG of 12-week streptozocin-induced diabetic rats, co nfirming the previous work. Anterograde and retrograde axonal transpor t of p75NTR within the sciatic nerve was similarly decreased in diabet ic rats, while levels of transport of trkA were unaffected. Treatment with systemic NGF reversed the diabetes-induced deficit in p75(NTR) tr anscripts and protein within the DRG and Left expression levels of trk A unchanged. We propose that in sensory neurons of diabetic rats, the ability to capture and retrogradely transport NGF may be impaired beca use of suboptimal production of p75(NTR) receptors and that NGF therap y may-overcome this deficiency.