360 Age-Related Changes in Splenic Neurotrophin Content: A Possible Cause for Declining Sympathetic Innervation in Old Rats

Abstract

Previous research in our laboratory demonstrated an age-related decline of noradrenergic (NA) sympathetic innervation in the spleens of male Fisher 344 (F344) rats, evident by 17 months of age that was not observed in 24-month-old male Brown Norway (BN) rats. Since, the growth and maintenance of mature sympathetic neurons is dependent on the synthesis of neurotrophic factors by a variety of cell types in target organs, we hypothesized that altered neurotrophic concentrations in spleens from aged F344 rats, but not in BN rats, may account for the strain-dependent differences. To test this hypothesis, total and free nerve growth factor (NGF) and neurotrophin-3 (NT-3) concentrations in spleens from young (3-month-old) and old male F344 (24-month-old) and BN (27-month-old) rats were determined by ELISA and correlated with splenic norepinephrine concentrations. Data were expressed as means + SEM, with subsequent Student's t-test performed to determine age-related difference (p≤0.05). In young adult F344 and BN rats the mean splenic concentrations of NT-3 and NGF were comparable to levels reported by other investigators. There was no effect of age on total splenic NGF concentrations (unbound + receptor bound) in either rat strain (p≥0.05). Unbound NGF concentrations in spleens from old F344 rats, and the ratio of free/bound NGF were significantly lower (p≤0.05) compared with young F344 controls. There was an age-related trend toward lower free NGF content in spleens from BN rats, but this was not statistically significant (p≥0.05). Conversely, the concentrations of free NT-3 in spleens from old F344 and BN rats were higher compared with young rats (p≤0.05). Age-associated changes in splenic neurotrophin content correlated with changes in splenic norepinephrine content. Collectively, these findings indicate altered neurotrophin expression in the aged spleen that may contribute to the previously reported strain-related differences in the density of sympathetic nerves in lymphoid compartments of the spleen with advancing age.

Sympathetic modulation of immunity: Relevance to disease

“…Spleen cells from NGF transgenic mice display lower splenic mitogen-induced proliferative responses, suggesting that increased NGF expression and/or NGF-induced increase in sympathetic innervation have consequences for immune responses. In contrast, with advancing age splenic NA nerves are lost in Fischer 344 (F344), Lewis and Brown-Norway rats concomitantly with a decline in splenic NGF concentrations [107].…”