We have examined the hypothesis that differences in NGF uptake and transport determine vulnerability to age-related neurodegeneration. Neurons projecting to cerebral blood vessels (CV) have been found to be more vulnerable to this kind of degeneration than those projecting to the iris. Uptake of NGF was therefore examined in sympathetic neurons projecting from the superior cervical ganglion (SCG) to CV and iris in young and old rats by treating the peripheral processes of these neurons with different doses of I125-NGF. Total uptake of I125-NGF (cpm per ganglion) was reduced in old rats following treatment of CV, but not iris, neurons. Numbers of labelled neurons were counted in autoradiographic preparations of sectioned ganglia. Data showed age-related reductions in numbers of labelled sympathetic and sensory neurons projecting to CV, but no change in numbers of neurons projecting to iris. Calculation of uptake of I125-NGF per neuron showed no major age-related differences. However, uptake per neuron was considerably lower for CV-projecting, compared to iris-projecting, SCG neurons. Counts of SCG neurons using a physical disector following retrograde tracing with fluorogold confirmed the selective vulnerability of CV-projecting neurons by showing a loss of these neurons in the period between 15 and 24m, contrasting with no change in numbers of iris-projecting neurons. We conclude that vulnerability to age-related neurodegeneration leading to neuronal cell death is associated with life-long low levels of NGF uptake while, conversely, life-long high levels of NGF uptake are associated with protection from age-related neurodegeneration.
cerebral blood vessels