Effect of nerve growth factor treatment on p75NTR gene expression in lumbar dorsal root ganglia of streptozocin-induced diabetic rats.
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.
Delcroix
J D
JD
Department of Pharmacology, St. Bartholomews' and Royal London Hospital School of Medicine and Dentistry, Queen Mary and Westfield College, University of London, UK.
Michael
G J
GJ
Priestley
J V
JV
Tomlinson
D R
DR
Fernyhough
P
P
D000818:Animals; D001370:Axonal Transport; D001692:Biological Transport; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism*; D005727:Ganglia, Spinal / Q000378:metabolism*; D015870:Gene Expression; D007150:Immunohistochemistry; D008297:Male; D009409:Nerve Crush; D009414:Nerve Growth Factors / Q000494:pharmacology*; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D020794:Receptor Protein-Tyrosine Kinases / Q000378:metabolism; D020800:Receptor, Nerve Growth Factor; D020917:Receptor, trkA; D017475:Receptors, Nerve Growth Factor / Q000032:analysis / Q000235:genetics* / Q000378:metabolism; D012584:Sciatic Nerve / Q000378:metabolism
D009414:Nerve Growth Factors; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; D020800:Receptor, Nerve Growth Factor; D017475:Receptors, Nerve Growth Factor; D020794:Receptor Protein-Tyrosine Kinases; D020917:Receptor, trkA