Alterations in sympathetic noradrenergic innervation in lymphoid organs with age

Previous work in our laboratories has shown a selective age-related loss of sympathetic noradrenergic (NA) nerves from the spleen and lymph nodes of rats. In contrast, NA nerve fiber density is dramatically increased in the thymus of aged mice and rats. We hypothesize that the diminished splenic NA innervation in old rats is due to cumulative oxidative metabolic autodestruction of NA nerve terminals by high concentrations of norepinephrine released during specific time periods of immunologic reactivity. These old animals show a loss of NK cell activity, diminished T-cell proliferation, and diminished cell-mediated immunity. To assess the plasticity of NA nerve fibers in the aged rat spleen, male Fischer 344 rats at 24 months of age were treated for 2 months with daily injections of 0.25 or 1.0 mg/kg/day of L-deprenyl, followed by a 10-day drug washout period. The L-deprenyl-treated rats showed a remarkable sprouting of NA nerves into the splenic white pulp, with regrowth into appropriate vascular and parenchymal compartments. Rats with enhanced NA nerve regrowth showed increased IL-2 and IFN-gamma production and NK cell activity compared with vehicle injected or uninjected age-matched control rats. We proposed that L-deprenyl stimulates NA nerve regrowth into secondary lymphoid organs, which leads to partial recovery of measures of immunosenescence.