ALTERATIONS IN SYMPATHETIC INNERVATION OF THYMUS AND SPLEEN IN AGED MICE

Aging is associated with reduced immune reactivity, contributing to in creased rates of infectious disease and cancer in old age. We have beg un to assess the potential for sympathetic nervous system involvement in age-related immune dysfunction by characterizing sympathetic noradr energic (NA) innervation in lymphoid organs in old animals. In the pre sent study noradrenergic innervation of spleen and thymus was examined histologically and neurochemically in 2-, 12- and 24-month old BALB/c mice. In the thymus of 2-month old animals, NA nerve fibers were foun d in the subcapsular, cortical, and cortico-medullary regions associat ed with blood vessels and septa; occasional branches from these nerve fibers entered the parenchyma. With increasing age and thymic involuti on, NA nerve fibers increased in density; by 24 months of age, dense p lexuses were compacted among septa and blood vessels, and numerous lin ear, varicose nerve fibers were observed branching into the parenchyma . Thymic norepinephrine (NE) concentration (per mg wet weight) increas ed approximately 4-fold in 12-month old animals and 15-fold in 24-mont h old animals. Taking the reduced thymus weight into account, total th ymic NE at 12- and 24-month of age was equivalent to total thymic NE a t 2-month of age, suggesting that NA innervation is maintained as the thymus involutes. In the spleen from 2-month old animals, NA innervati on entered the white pulp with the central artery to innervate the per iarteriolar lymphatic sheath and the marginal zone. At 12-month of age , histologically and neurochemically there was no change in splenic NA innervation. By 24-month of age, NE was increased significantly, inde pendent of changes in spleen weight. Histologically, increased catecho lamine-containing fibers were apparent at 24-month of age, particularl y in the parenchyma surrounding the central artery. The alterations in sympathetic NA innervation of lymphoid organs with age suggest that t he sympathetic nervous system and NE may play a role in age-associated immune dysregulation. Alternatively, the changes in NA innervation ma y be secondary to functional changes within the immune system. (C) 199 7 Elsevier Science Ireland Ltd.