REGULATION OF RAT SYMPATHETIC-NERVE DENSITY BY TARGET TISSUES AND NGFIN MATURITY AND OLD-AGE

Previous studies in our laboratory using a transplantation model have shown that target tissues of some autonomic neurons, including cerebra l blood vessels, exert a controlling influence on nerve fibre loss in old age. The present study was undertaken in order to discover whether the influence of targets extends to controlling age changes in specif ic populations of nerves. In old rats, we have demonstrated a signific ant decrease of similar to 50% in the sympathetic innervation of middl e cerebral arteries, using tyrosine hydroxylase-like immunoreactivity. Following transplantation, tyrosine hydroxylase-like immunoreactive n erve density on both young and old implanted middle cerebral arteries mirrored the nerve densities seen in normal, non-transplanted vessels. Furthermore, implanted tissue from old donors became reinnervated wit h a nerve density similar to 50% less than that of young implanted ves sels. Treatment of transplants with nerve growth factor, however, was able to reverse these age changes and restore the sympathetic innervat ion of aged middle cerebral arteries to levels above those seen in you ng middle cerebral arteries. These results suggest that the pattern an d density of sympathetic innervation that the middle cerebral artery r eceives is determined by the target rather than by the neurons supplyi ng the tissue. The ability of nerve growth factor to induce regrowth i n sympathetic neurons innervating ageing target tissues implies that a ge-related neuronal atrophy may be due to reduced synthesis or availab ility of target-derived neurotrophic factors.