title: 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. 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 F344 rats, the traditional animal model for aging research. Splenic sympathetic neurotransmission was evaluated between 8 and 32 months of age by assessing (1) NA nerve fiber density, (2) splenic norepinephrine (NE) concentration, and (3) circulating catecholamine levels after decapitation. We report a decline in NA nerve density in splenic white pulp (45%) at 15 months of age compared with 8-month-old (M) rats, which is followed by a much slower rate of decline between 24 and 32 months. Lower splenic NE concentrations between 15 and 32 months of age compared with 8M rats were consistent with morphometric findings. Circulating catecholamine levels after decapitation stress generally dropped with increasing age. These findings suggest there is a sympathetic-to-immune system dysregulation beginning at middle age. Given the unique T-helper-2 bias in BN rats, altered sympathetic-immune communication may be important for understanding the age-related rise in asthma and autoimmunity.
authors.affiliation: Department of Physiology and Pharmacology, Loma Linda University School of Medicine, Loma Linda, CA 92350, USA.
authors.forename: Sam D
authors.initials: SD
authors.lastname: Perez
authors.forename: Dorian
authors.initials: D
authors.lastname: Silva
authors.forename: Ashley Brooke
authors.initials: AB
authors.lastname: Millar
authors.forename: Christine A
authors.initials: CA
authors.lastname: Molinaro
authors.forename: Jeff
authors.initials: J
authors.lastname: Carter
authors.forename: Katie
authors.initials: K
authors.lastname: Bassett
authors.forename: Dianne
authors.initials: D
authors.lastname: Lorton
authors.forename: Paola
authors.initials: P
authors.lastname: Garcia
authors.forename: Laren
authors.initials: L
authors.lastname: Tan
authors.forename: Jonathon
authors.initials: J
authors.lastname: Gross
authors.forename: Cheri
authors.initials: C
authors.lastname: Lubahn
authors.forename: Srinivasan
authors.initials: S
authors.lastname: Thyagarajan
authors.forename: Denise L
authors.initials: DL
authors.lastname: Bellinger
mesh_terms: D056704:Adaptive Immunity / Q000502:physiology; D000375:Aging / Q000502:physiology*; D000818:Animals; D001327:Autoimmune Diseases / Q000276:immunology / Q000503:physiopathology; D002395:Catecholamines / Q000032:analysis / Q000097:blood; D015536:Down-Regulation / Q000502:physiology; D007113:Immunity, Innate / Q000502:physiology; D008137:Longitudinal Studies; D008221:Lymphoid Tissue / Q000294:innervation*; D008297:Male; D015213:Neuroimmunomodulation / Q000502:physiology*; D009638:Norepinephrine / Q000032:analysis / Q000378:metabolism; D017729:Presynaptic Terminals / Q000378:metabolism / Q000648:ultrastructure; D051381:Rats; D011916:Rats, Inbred F344; D013045:Species Specificity; D013154:Spleen / Q000294:innervation* / Q000502:physiology; D017779:Sympathetic Fibers, Postganglionic / Q000033:anatomy & histology* / Q000378:metabolism; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology / Q000378:metabolism
chemical_list: D002395:Catecholamines; D009638:Norepinephrine