title: The release of sympathetic neurotransmitters is impaired in aged rats after an inflammatory stimulus: a possible link between cytokine production and sympathetic transmission.
abstract: Aging results in a general decline in the response to external insults, including acute inflammatory challenges. In young animals, the inflammatory response requires activation of the sympathetic system, including neurotransmitters such as ATP, and catecholamines (epinephrine and norepinephrine). To test whether aging affects activation of this axis, and whether this in turn might affect cytokine release, we administered lipopolysaccharide (LPS) i.p. to adult, middle-aged and aged Fisher 344 rats (6-, 15- and 23-month old, respectively) and evaluated the early (0-12h) serum levels of Neuropeptide-Y (NP-Y), ATP and vanillyl mandelic acid (VMA, as an indirect measurement of catecholamine levels). In addition, we evaluated the association between these factors and serum levels of the cytokines tumor necrosis factor-alpha (TNFalpha) and interleukin-10 (IL-10). Induction of both ATP and NP-Y was markedly reduced in the serum of aged animals, when compared to their younger counterparts, while induction of VMA was not affected by age. In spite of these changes, serum levels of TNFalpha and IL-10 were strongly hyper induced and delayed in aged rats. The results suggest that during aging there is a dysregulation in sympathetic neurotransmitter regulatory mechanisms, and this might play a role in the impairment of the inflammatory response.
authors.affiliation: Pontificia Universidad Católica de Chile, Casilla 114-D, Santiago, Chile.
authors.forename: Verónica
authors.initials: V
authors.lastname: Donoso
authors.forename: Christian R
authors.initials: CR
authors.lastname: Gomez
authors.forename: Miguel Angel
authors.initials: MA
authors.lastname: Orriantia
authors.forename: Viviana
authors.initials: V
authors.lastname: Pérez
authors.forename: Claudio
authors.initials: C
authors.lastname: Torres
authors.forename: Claudio
authors.initials: C
authors.lastname: Coddou
authors.forename: Pablo
authors.initials: P
authors.lastname: Nelson
authors.forename: Kevin
authors.initials: K
authors.lastname: Maisey
authors.forename: Bernardo
authors.initials: B
authors.lastname: Morales
authors.forename: Ricardo
authors.initials: R
authors.lastname: Fernandez
authors.forename: Mónica
authors.initials: M
authors.lastname: Imarai
authors.forename: Juan Pablo
authors.initials: JP
authors.lastname: Huidobro-Toro
authors.forename: Felipe
authors.initials: F
authors.lastname: Sierra
authors.forename: Claudio
authors.initials: C
authors.lastname: Acuña-Castillo
mesh_terms: D000255:Adenosine Triphosphate / Q000097:blood; D000375:Aging / Q000276:immunology* / Q000502:physiology*; D000818:Animals; D016207:Cytokines / Q000096:biosynthesis* / Q000097:blood; D007249:Inflammation / Q000276:immunology* / Q000503:physiopathology*; D016753:Interleukin-10 / Q000097:blood; D008070:Lipopolysaccharides / Q000633:toxicity; D008297:Male; D008959:Models, Neurological; D015213:Neuroimmunomodulation; D009478:Neuropeptide Y / Q000097:blood; D018377:Neurotransmitter Agents / Q000097:blood / Q000378:metabolism*; D051381:Rats; D011916:Rats, Inbred F344; D013564:Sympathetic Nervous System / Q000378:metabolism; D009435:Synaptic Transmission; D014409:Tumor Necrosis Factor-alpha / Q000097:blood; D014642:Vanilmandelic Acid / Q000097:blood
chemical_list: D016207:Cytokines; D008070:Lipopolysaccharides; D009478:Neuropeptide Y; D018377:Neurotransmitter Agents; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D014642:Vanilmandelic Acid; D000255:Adenosine Triphosphate