The role of NGF uptake in selective vulnerability to cell death in ageing sympathetic neurons

• Published in: The European journal of neuroscience Vol. 20; no. 11; pp. 2848 - 2856
• Main Authors: Gatzinsky, Kliment P., Thrasivoulou, Christopher, Campioni-Noack, Maddalena, Underwood, Clare, Cowen, Tim
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Science Ltd 01.12.2004
• Subjects: aged rats; Aging - metabolism; Animals; Autoradiography - methods; basal-forebrain; Cell Count - methods; Cell Death - physiology; cerebral blood vessels; cholinergic neurons; cognitive impairment; Dose-Response Relationship, Drug; Enzyme-Linked Immunosorbent Assay - methods; Fluorescent Dyes - metabolism; Iodine Isotopes - pharmacokinetics; iris; Iris - drug effects; Iris - innervation; Male; Nerve Growth Factor - metabolism; nerve growth-factor; neurodegeneration; Neurons - cytology; Neurons - metabolism; Neurosciences; neurotrophic hypothesis; neurotrophin receptors; Neurovetenskaper; old-age; rat; Rats; Rats, Sprague-Dawley; receptor gene-expression; regenerative changes; retrograde axonal transport; retrograde transport; Stilbamidines - metabolism; Superior Cervical Ganglion - cytology; Sympathetic Nervous System - cytology; Sympathetic Nervous System - physiology; Time Factors
• ISSN: 0953-816X; 1460-9568
• DOI: 10.1111/j.1460-9568.2004.03780.x

We have examined the hypothesis that differences in nerve growth factor (NGF) uptake and transport determine vulnerability to age‐related neurodegeneration. Neurons projecting to cerebral blood vessels (CV) in aged rats are more vulnerable to age‐related 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 was reduced in old CV‐projecting, but not iris‐projecting, neurons. Numbers of radiolabelled neurons projecting to each target were counted in sectioned ganglia. The data showed age‐related reductions in numbers of labelled neurons projecting to CV, but no change in numbers of neurons projecting to the iris. Calculation of uptake of I125‐NGF per neuron unexpectedly showed no major age‐related differences in either of the two neuron populations. However, uptake per neuron was considerably lower for young and old CV‐projecting, compared to iris‐projecting, SCG neurons. We hypothesized that variations in NGF uptake might affect neuronal survival in old age. Counts of SCG neurons using a physical disector following retrograde tracing with Fluorogold confirmed the selective vulnerability of CV‐projecting neurons by showing a significant 37% loss of these neurons in the period between 15 and 24 months. In contrast, there was no significant loss of iris‐projecting neurons. We conclude that vulnerability to, or protection from, age‐related neurodegeneration and neuronal cell death are associated with life‐long low, or high, levels of NGF uptake, respectively.