Sympathetic innervation of the spleen in male Brown Norway rats: A longitudinal aging study

Abstract

Aging leads to reduced cellular immunity with consequent increased rates of infectious disease, cancer and autoimmunity in the elderly. The sympathetic nervous system (SNS) modulates innate and adaptive immunity via innervation of lymphoid organs. In aged Fischer 344 (F344) rats, noradrenergic (NA) nerve density in secondary lymphoid organs declines, which may contribute to immunosenescence with aging. These studies suggest there is SNS involvement in age-induced immune dysregulation. Objectives The purpose of this study was to longitudinally characterize age-related change in sympathetic innervation of the spleen and sympathetic activity/tone in male Brown Norway (BN) rats, which live longer and have a strikingly different immune profile than the F344 rat, the traditional animal model for aging research. Methods Splenic sympathetic neurotransmission was evaluated between 8 and 32 months of age by (1) NA nerve fiber density; (2) splenic norepinephrine (NE) concentration; and (3) circulating catecholamines levels after decapitation. Results We report a decline in noradrenergic nerve density in splenic white pulp (45%) at 18 months of age compared with 8 month-old (M) rats, which is followed by a much slower rate of decline between 18 and 32 months. Lower splenic NE concentrations were consistent with morphometric findings. Circulating catecholamines levels generally dropped with increasing age. Conclusion These findings suggest there is a sympathetic-to-immune system dysregulation beginning at middle age. Given the unique T-helper-2 bias in Brown Norway rats, altered sympathetic-immune communication may be important for understanding the age-related rise in asthma and autoimmunity.

Distribution of non-myelinating Schwann cells and their associations with leukocytes in mouse spleen revealed by immunofluorescence staining

“…Some previous reports 9 , 19 , 31 have shown that noradrenergic innervation is particularly rich in T-cell zones and in areas of mast cells/macrophages, whereas the follicular and nodular zones in which B cells mature, are poorly innervated. Scattered nerve fibers have been observed in the red pulp primarily associated with plexuses along the trabeculae.…”

“… 9 , 10 , 15-20 Noradrenergic postganglionic nerve fibers enter the spleen with the splenic artery, run along the trabeculae in plexuses, extend into the white pulp along the central artery and end in the periarterial lymphatic sheath. 9 , 19 , 31 Additionally, some studies have provided evidence for existence of the parasympathetic innervation of the spleen. 9 However, the courses of the sympathetic nerves and parasympathetic nerves might be different.…”

Increased pain and sensory hyperinnervation of the ligamentum flavum in patients with lumbar spinal stenosis

“…Patients with disc herniation were clearly younger than patients with LSS, and this might interfere with our results. However, during aging, nerve fiber density remains constant [44][45][46] or decreases, 47,48 but there are no data that demonstrate increased nerve fiber density during aging. From this point of view, the older LSS patients compared to the younger controls should have had a similar or a lower density of nerve fibers, but the opposite was found.…”

Age-Associated Remodeling of Neural and Nonneural Thymic Catecholaminergic Network Affects Thymopoietic Productivity

“…Given that there is an age-related drop in the plasma CA levels after decapitation stress [112] , the rise in the thymic NA level with age [55-57, 60, 61] cannot be ascribed to the changes in circulating CA levels. However, Bellinger et al [113] found that the density of noradrenergic nerve fibers progressively rises with age in thymi of Fisher 344 rats, so it was profoundly increased in middleaged compared with young adult animals.…”