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l-Deprenyl Reverses Age-Associated Decline in Splenic Norepinephrine, Interleukin-2 and Interferon-γ Production in Old Female F344 Rats
ThyagaRajan S. ·
Madden K.S. ·
Boehm G.W. ·
Stevens S.Y. ·
Felten D.L. ·
Neuroimmunomodulation 2013;20:72–78 (DOI: 10.1159/000345043)
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. Objectives: 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.
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