3-aminobenzamide prevents restraint-evoked immunocompromise.
Chronic stressors compromise immune function, which may affect disease state in rats and mice. Although the molecular mechanism(s) underlying the link between psychological stressors and physiological responses remain elusive, one putative mechanism is oxidative stress. DNA damage activates poly(ADP-ribose) polymerase (PARP), a nuclear enzyme that participates in DNA repair; if DNA damage is extensive, however, then PARP becomes cytotoxic. Because PARP-1-/- transgenic mice are resistant to chronic stress-induced immunocompromise, we tested the hypothesis that pre-restraint administration of 3-aminobenzamide (3-AB), a PARP inhibitor, would prevent restraint-evoked suppression of antibody production to the novel protein, keyhole limpet hemocyanin (KLH). Mice were physically restrained for 3 h daily for 14 consecutive days, then immunized with KLH. Daily restraint continued for an additional 21 days and anti-KLH IgG production was assessed. Mice exposed to repeated restraint reduced concentrations of anti-KLH IgG, whereas, mice treated with 3-AB (0.5, 5.0, or 20.0 mg/kg) prior to each bout of restraint displayed anti-KLH IgG concentrations similar to those of unrestrained mice. Treatment with 3-AB (0.5 and 5.0 mg/kg) during the restraint paradigm also facilitated habituation of the corticosterone response to restraint, and 3-AB (0.5 mg/kg) reduced the effect of repeated restraint on body mass. However, the immunoprotective effects of 3-AB and the endocrine and metabolic effects appear to be distinctly regulated because, unlike the endocrine and metabolic effects, the immunoprotective effects of 3-AB were independent of dose. These data suggest that PARP inhibitors may be useful to prevent compromised immune function in response to stressors.
Neigh
Gretchen N
GN
Department of Psychology, Institute for Behavioral Medicine Research, The Ohio State University, Columbus, OH 43210, USA. gmccand@emory.edu
Samuelsson
Andrew R
AR
Bowers
Stephanie L
SL
Nelson
Randy J
RJ
D000704:Analysis of Variance; D000818:Animals; D000917:Antibody Formation / Q000187:drug effects; D001549:Benzamides / Q000008:administration & dosage*; D003345:Corticosterone / Q000097:blood; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000008:administration & dosage*; D006185:Habituation, Psychophysiologic / Q000502:physiology; D006433:Hemocyanins / Q000276:immunology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases / Q000187:drug effects / Q000276:immunology*; D011897:Random Allocation; D012149:Restraint, Physical / Q000502:physiology; D013315:Stress, Psychological / Q000097:blood / Q000201:enzymology* / Q000276:immunology*
D001549:Benzamides; D004791:Enzyme Inhibitors; C025160:3-aminobenzamide; D006433:Hemocyanins; C499321:Parp1 protein, mouse; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases; C032808:keyhole-limpet hemocyanin; D003345:Corticosterone