title: Sympathetic nervous system and lymphocyte proliferation in the Fischer 344 rat spleen: a longitudinal study.
abstract: Aging is associated with reduced cellular immunity, which leads to increased rates of infectious disease, cancer and autoimmunity in the elderly. Previous findings from our laboratory revealed an age-related decline in sympathetic innervation of immune organs that affects immunity. These studies suggested potential sympathetic nervous system involvement in age-induced immune dysregulation.
  
  
  OBJECTIVE
  The purpose of this study was to longitudinally characterize the effects of age on sympathetic neurotransmission in the spleen and net sympathetic activity/tone in male Fischer 344 rats.
  
  
  METHODS
  Splenic sympathetic neurotransmission was evaluated between 8 and 24 months of age by (1) splenic norepinephrine (NE) concentration and turnover, (2) beta-adrenergic receptor (beta-AR) expression and (3) beta-AR-stimulated splenocyte cAMP production. Measures of sympathetic neurotransmission were correlated with age-related changes in Concanavalin A (Con A)-stimulated splenocyte proliferation.
  
  
  RESULTS
  Splenic NE turnover increased during middle age, then subsequently declined by 18 months of age compared with 8-month-old controls (young). Splenic NE concentration increased at 10 months and decreased at 18-24 months, compared with young rats; however, plasma NE levels were not affected by age. Plasma epinephrine levels were decreased at 24 months. NE synthesis blockade increased and decreased the rate of plasma catecholamine depletion in middle and old age, respectively. beta-AR-stimulated cAMP production increased in splenocytes by 15 months. An age-related decrease in Con A-induced splenocyte proliferation was apparent by 10 months and persisted through 24 months. The decline in Con A-induced splenocyte proliferation correlated with the age-related increase in cAMP production.
  
  
  CONCLUSIONS
  Aging alters sympathetic nervous system metabolism in the spleen to affect beta-AR signaling to splenocytes, suggesting that altered sympathetic-immune modulation changes are evident by early middle age.
authors.affiliation: Department of Pathology and Human Anatomy, Loma Linda University School of Medicine, Loma Linda, CA 92350, USA. dbellinger@llu.edu
authors.forename: Denise L
authors.initials: DL
authors.lastname: Bellinger
authors.forename: Dorian
authors.initials: D
authors.lastname: Silva
authors.forename: Ashley Brooke
authors.initials: AB
authors.lastname: Millar
authors.forename: Christine
authors.initials: C
authors.lastname: Molinaro
authors.forename: Mark
authors.initials: M
authors.lastname: Ghamsary
authors.forename: Jeff
authors.initials: J
authors.lastname: Carter
authors.forename: Sam
authors.initials: S
authors.lastname: Perez
authors.forename: Dianne
authors.initials: D
authors.lastname: Lorton
authors.forename: Cheri
authors.initials: C
authors.lastname: Lubahn
authors.forename: Gerson
authors.initials: G
authors.lastname: Araujoa
authors.forename: Srinivasan
authors.initials: S
authors.lastname: Thyagarajan
mesh_terms: D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D000375:Aging / Q000276:immunology*; D000818:Animals; D003208:Concanavalin A / Q000494:pharmacology; D000242:Cyclic AMP / Q000096:biosynthesis; D016207:Cytokines / Q000096:biosynthesis; D004837:Epinephrine / Q000097:blood; D007545:Isoproterenol / Q000494:pharmacology; D008213:Lymphocyte Activation / Q000187:drug effects; D008297:Male; D015213:Neuroimmunomodulation / Q000502:physiology*; D009638:Norepinephrine / Q000378:metabolism; D051381:Rats; D011916:Rats, Inbred F344; D011943:Receptors, Adrenergic, beta / Q000378:metabolism; D013154:Spleen / Q000166:cytology / Q000276:immunology* / Q000294:innervation / Q000378:metabolism; D013564:Sympathetic Nervous System / Q000502:physiology*; D016176:T-Lymphocyte Subsets / Q000187:drug effects / Q000276:immunology; D014446:Tyrosine 3-Monooxygenase / Q000037:antagonists & inhibitors; D019805:alpha-Methyltyrosine / Q000494:pharmacology
chemical_list: D016207:Cytokines; D011943:Receptors, Adrenergic, beta; D003208:Concanavalin A; D019805:alpha-Methyltyrosine; D000242:Cyclic AMP; D014446:Tyrosine 3-Monooxygenase; D007545:Isoproterenol; D015056:1-Methyl-3-isobutylxanthine; D009638:Norepinephrine; D004837:Epinephrine