Retrograde axonal transport of intravenously administered 125I-nerve growth factor in rats with streptozotocin-induced diabetes.
We have previously demonstrated a reproducible axonopathy, involving but not confined to sympathetic neurons, which involves selectively the mesenteric nerves of chronically diabetic rats. We describe a series of experiments aimed at correlating changes in the retrograde transport of 125I-nerve growth factor (125I-NGF) with development of the lesions. 125I-NGF was injected systemically and the time course of accumulation compared in superior cervical ganglion (SCG) and superior mesenteric ganglion (SMG). 125I-NGF accumulated in the SCG with a sharp peak at 12 h, whereas in the SMG, accumulation reached a plateau, remaining at relatively constant amounts for 8 h before decreasing. There was a marked decrease in the accumulation of 125I-NGF (averaging 44% in 11 separate experiments) in the SMG at early times (approximately 12 h). These decreases were seen in animals diabetic for times ranging from 2 days to 10 mo. In contrast, no consistent decrease was observed in the SCG. The time course of 125I-NGF accumulation was unaltered in the SCG of diabetic rats but was clearly retarded in the SMG of diabetic animals. Morphometric examination of the SMG of diabetic animals and controls showed little or no atrophy or neuron loss due to diabetes. We conclude that decreases in the retrograde transport of NGF occur selectively in those ganglia (SMG) serving the alimentary tract in which mesenteric nerves develop distal axonopathy, but not in ganglia whose nerves do not ultimately develop such lesions (SCG). The decreases in retrograde transport precede the development of morphologic lesions in this system. These results are consistent with the suggestion that impairment of axonal transport may play a role in the development of axonopathy.
D000818:Animals; D001369:Axons / Q000378:metabolism*; D001692:Biological Transport; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism*; D003929:Diabetic Neuropathies / Q000209:etiology; D005728:Ganglia, Sympathetic / Q000033:anatomy & histology / Q000378:metabolism*; D007275:Injections, Intravenous; D007328:Insulin / Q000627:therapeutic use; D008297:Male; D008643:Mesentery / Q000294:innervation; D009409:Nerve Crush; D009414:Nerve Growth Factors / Q000008:administration & dosage*; D051381:Rats; D011919:Rats, Inbred Strains; D013997:Time Factors
D007328:Insulin; D009414:Nerve Growth Factors