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The aim of this study was to investigate whether NGF could reverse the nerve fiber atrophy exhibited by some neurons in old age. We used quantitative immunohistochemical techniques to investigate how the autonomic nerves that supply different blood vessels are affected by aging. Age changes in the nerve plexus were not widespread but were specific to particular vascular targets. Furthermore, where nerve fiber atrophy did occur, it affected different populations of nerves; specifically, sympathetic nerve fibers were lost from the middle cerebral artery while nonsympathetic nerves were lost from the tail vein. Peripheral target tissues have been shown to have a trophic influence on the pattern and density of their innervation, which declines in old age (Gavazzi et al., 1992), possibly as a result of decreased availability of neurotrophic factors such as NGF. Consequently, in an attempt to reverse nerve fiber atrophy, we used miniosmotic pumps to infuse NGF for 2 weeks over involuting nerve fibers in the middle cerebral artery of freely moving aged rats. Our results show that exogenous NGF can induce organotypic neurite outgrowth from aged neurons undergoing nerve fiber atrophy. Moreover, NGF can induce a change in the pattern of the old nerve plexus to one similar to that seen in young animals. NGF had different effects on the extent and manner of neurite outgrowth in young and aged nerves. NGF induced greater nerve growth in old compared to young nerves, causing old nerves to grow within existing nerve bundles and to sprout new nerve fibers, in contrast to young nerves, which tended to grow only within existing nerve bundles. In conclusion, this study shows the potential of exogenous NGF to reverse age-related changes in neuronal morphology.

In vivo infusion of NGF induces the organotypic regrowth of perivascular nerves following their atrophy in aged rats