Axonal transport of endogenous nerve growth factor (NGF) and NGF receptor in experimental diabetic neuropathy.
There is increasing evidence that deprivation of the retrogradely transported neurotrophic protein nerve growth factor (NGF) accounts for some functional deficits known to occur in experimental diabetic neuropathy. Here we have studied changes in the axonal transport of endogenous NGF, NGF receptor (NGFR), and NGFR saturation (NGF/NGFR ratio) in the rat sciatic nerve after 2 months of streptozotocin (STZ)-induced diabetes mellitus. Compared with vehicle-treated control rats (blood glucose: 6-12 mM), there was a very clear reduction in the retrograde transport of NGF by 50% (P < 0.001) in STZ-treated, diabetic animals (blood 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 observed 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 was observed in the STZ-poor responders. Moreover, the NGFR saturation and amount of retrogradely transported NGF were negatively correlated to the individual glucose concentration in diabetics (r2 = 0.47 and 0.55, respectively; P < 0.0001). These findings indicate that, while NGFR expression is normal in the STZ-diabetic neuropathy model, the marked decrease in receptor saturation observed in diabetics may reflect low peripheral NGF levels, which in consequence leads to the apparent deprivation of neuronal NGF in diabetic rats.
Hellweg
R
R
Department of Psychiatry, Free University of Berlin, Germany.
Raivich
G
G
Hartung
H D
HD
Hock
C
C
Kreutzberg
G W
GW
D000818:Animals; D001369:Axons / Q000378:metabolism*; D001692:Biological Transport; D001786:Blood Glucose / Q000032:analysis; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism; D003929:Diabetic Neuropathies / Q000378:metabolism*; D008297:Male; D009414:Nerve Growth Factors / Q000378:metabolism*; D009994:Osmolar Concentration; D051381:Rats; D017208:Rats, Wistar; D017475:Receptors, Nerve Growth Factor / Q000378:metabolism*; D012584:Sciatic Nerve / Q000378:metabolism
D001786:Blood Glucose; D009414:Nerve Growth Factors; D017475:Receptors, Nerve Growth Factor