Age-related decrease in sympathetic sprouting is primarily due to decreased target receptivity: implications for understanding brain aging.

Abstract

Aging of the nervous system is characterized by reduced anatomical plasticity. The cause of this decreased plasticity is not known because it is usually not possible to distinguish between extrinsic and intrinsic factors that affect neuronal growth. One example of age-related reduced neuronal plasticity that is amendable to such analysis is the growth of sympathetic axons into the rat hippocampal formation following septal denervation. This sprouting response can be elicited throughout the lifespan of the rat but is drastically reduced in aged animals. The age-related reduction in ingrowth could theoretically be due to decreased receptivity of the target (reduced trophic support or increased inhibition of growth), decreased responsivity of the sympathetic neurons or a combination of both factors. In order to test the relative contributions of the age of the target tissue and the age of the sympathetic neurons to the reduced growth observed in aged animals, superior cervical ganglia were transplanted from young animals into old animals (y/o) and from old animals into young animals (o/y) as well as autologously within the same animals (y/y and o/o). The extent of sympathetic ingrowth and the survival of transplanted neurons were assessed with fluorescence histochemical methods. The extent of ingrowth was significantly greater in young hosts compared with old hosts regardless of the age of the donor. In addition, the survival of transplanted neurons was greater in younger hosts than in aged hosts regardless of donor age. These results indicate that sympathetic ingrowth is reduced in aging primarily because of decreased receptivity of the hippocampal target tissue.