title: L-Deprenyl reverses age-associated decline in splenic norepinephrine, interleukin-2 and interferon-γ production in old female F344 rats.
abstract: Aging in female rats is associated with cessation of reproductive cycles, development of mammary cancer, and increased incidence of autoimmune diseases. Previously, we demonstrated an age-related decline in sympathetic noradrenergic (NA) innervation in the spleen and lymph nodes of female F344 rats accompanied by significantly reduced natural killer cell activity, interleukin (IL)-2 and interferon (IFN)-γ production, and T- and B-cell proliferation, suggesting possible links between sympathetic activity and immunosenescence.
  
  
  OBJECTIVE
  The aim of this study is to investigate the effects of L-(-)-deprenyl, a monoamine oxidase-B inhibitor, on the sympathetic nervous system and cell-mediated immune responses in old female rats.
  
  
  METHODS
  Low doses of L-deprenyl (0.25 or 1.0 mg/kg body weight, BW) were administered intraperitoneally to 19- to 21-month-old female F344 rats for 8 weeks. To assess the stereoselectivity of the effects of deprenyl on splenic sympathetic activity and immune responses, the D-enantiomer (D-(+)-deprenyl; 1.0 mg/kg BW) was also included in the studies. Norepinephrine (NE) concentration and content, and mitogen-induced T-cell proliferation and cytokine production were assessed in the splenocytes after deprenyl treatment.
  
  
  RESULTS
  Treatment with L-deprenyl reversed the age-related decrease in NE concentration and content and IFN-γ production, and increased IL-2 production in the spleen while D-deprenyl did not affect the age-associated reduction in splenic NE levels or cytokine production.
  
  
  CONCLUSIONS
  These findings demonstrate that L-deprenyl exerts neurorestorative and immunostimulatory effects on the sympathetic nervous system and cell-mediated immune responses during aging and provides evidence for a causal relationship between some aspects of immunosenescence and the age-related decline in sympathetic nerves in the spleens of female F344 rats.
authors.affiliation: Department of Pathology and Human Anatomy, Loma Linda University School of Medicine, Loma Linda, CA, USA.
authors.forename: Srinivasan
authors.initials: S
authors.lastname: Thyagarajan
authors.forename: Kelley S
authors.initials: KS
authors.lastname: Madden
authors.forename: Gary W
authors.initials: GW
authors.lastname: Boehm
authors.forename: Suzanne Y
authors.initials: SY
authors.lastname: Stevens
authors.forename: David L
authors.initials: DL
authors.lastname: Felten
authors.forename: Denise L
authors.initials: DL
authors.lastname: Bellinger
mesh_terms: D000375:Aging / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D000818:Animals; D002851:Chromatography, High Pressure Liquid; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D007111:Immunity, Cellular / Q000187:drug effects / Q000276:immunology; D007371:Interferon-gamma / Q000096:biosynthesis; D007376:Interleukin-2 / Q000096:biosynthesis; D018696:Neuroprotective Agents / Q000494:pharmacology*; D009638:Norepinephrine / Q000096:biosynthesis; D051381:Rats; D011916:Rats, Inbred F344; D012642:Selegiline / Q000494:pharmacology*; D013154:Spleen / Q000187:drug effects* / Q000276:immunology* / Q000378:metabolism; D013564:Sympathetic Nervous System / Q000187:drug effects / Q000276:immunology
chemical_list: D007376:Interleukin-2; D018696:Neuroprotective Agents; D012642:Selegiline; D007371:Interferon-gamma; D009638:Norepinephrine