Autonomic nervous system as a model of neuronal aging: the role of target tissues and neurotrophic factors.

The aim of this study was to determine the role of target tissues and neurotrophic factors in the growth and atrophy of autonomic neurons during development and aging. Using quantitative neuroanatomical techniques, it is shown that, although axonal and dendritic growth is apparent throughout postnatal development, different patterns of growth are found in autonomic neurons innervating different target tissues. For example, sympathetic neurons innervating the submandibular gland continue to grow well into maturity, but those innervating the iris cease net growth early in postnatal development. Similarly, although neuronal atrophy was observed in aged autonomic ganglia, this was not a general phenomenon but was specific to neurons innervating particular target tissues. Sympathetic neurons innervating the middle cerebral artery showed significant axonal and dendritic atrophy in old age, whereas neurons innervating the iris were morphologically unchanged. The trophic influence of peripheral target tissues on their innervating neurons has been shown to decline in old age possibly as a result of decreased availability of target-derived neurotrophic factors such as nerve growth factor (NGF) [Gavazzi et al. (1992) Neuroreport, 3:717-720]. Therefore, in an attempt to reverse neuronal atrophy where it occurred, NGF was infused via miniosmotic pumps over the peripheral axons of aged neurons. NGF induced increases in soma size, dendritic length and axonal arborization. However, in contrast to young adult neurons, no increase in the number of dendritic branch points or primary dendrites was observed, suggesting that some aspects of neuronal plasticity are impaired in old age. In sum, these results show a range of age- and target-specific differences in the axonal and dendritic morphology of autonomic neurons that may result from differing trophic interactions with their target tissues.