Diabetes and axotomy-induced deficits in retrograde axonal transport of nerve growth factor correlate with decreased levels of p75 LNTR protein in lumbar dorsal root ganglia

Abstract

The effect of sensory neurone axotomy on the level of retrograde axonal transport of nerve growth factor (NGF) was studied in the sciatic nerve of age-matched normal and 8-week streptozocin-diabetic rats. In normal rats a 10-day sciatic nerve crush induced a 41% decrease in transported NGF, however, axotomy of sensory neurones of diabetic rats did not significantly effect the already deficient levels of NGF undergoing retrograde transport. At first sight, this result indicated that transported NGF levels in the sciatic nerve of diabetic rats are at a residual level due to deficient availability of target-derived NGF. To confirm this, the relationship of the transported NGF to the level of sensory neurone expression of the NGF receptor proteins was analysed. Western blots of L 4 and L 5 dorsal root ganglia (DRG) homogenates revealed no effect of axotomy and/or diabetes on the levels of the 145-kDa tyrosine kinase form of trkA. However, the expression of p75 LNTR protein in the intact DRG was reduced in diabetic compared with normal rats (56%; P<0.01), and axotomy reduced the levels in the ipsilateral ganglia of normal but not diabetic rats – as seen for NGF axonal transport. Reductions in retrograde axonal transport of NGF in both diabetes and/or axotomy were associated with the levels of p75 LNTR within the lumbar DRG.