AXONAL-TRANSPORT OF ENDOGENOUS NERVE GROWTH-FACTOR (NGF) AND NGF RECEPTOR IN EXPERIMENTAL DIABETIC NEUROPATHY

There is increasing evidence that deprivation of the retrogradely tran sported neurotrophic protein nerve growth factor (NGF) accounts for so me functional deficits known to occur in experimental diabetic neuropa thy. Here we have studied changes in the axonal transport of endogenou s NGF, NGF receptor (NGFR), and NGFR saturation (NGF/NGFR ratio) in th e rat sciatic nerve after 2 months of streptozotocin (STZ)-induced dia betes mellitus. Compared with vehicle-treated control rats (blood gluc ose: 6-12 mM), there was a very clear reduction in the retrograde tran sport of NGF by 50% (P < 0.001) in STZ-treated, diabetic animals (bloo d glucose: 33-62 mM). No significant reduction in NGF axonal transport was observed in a subpopulation of STZ-treated rats (poor responders) with nearly normal glucose levels (range: 9-12 mM). No change was obs erved in any group in the retrograde transport of NGFR. Compared with control rats, however, the apparent NGFR saturation was reduced by 45% (P < 0.002) in STZ diabetics, whereas no change in NGFR saturation wa s observed in the STZ-poor responders. Moreover, the NGFR saturation a nd amount of retrogradely transported NGF were negatively correlated t o the individual glucose concentration in diabetics (r(2) = 0.47 and 0 .55, respectively; P < 0.0001). These findings indicate that, while NG FR expression is normal in the STZ-diabetic neuropathy model, the mark ed decrease in receptor saturation observed in diabetics may reflect l ow peripheral NGF levels, which in consequence leads to the apparent d eprivation of neuronal NGF in diabetic rats. (C) 1994 Academic Press, Inc.