A negative feedback loop exists between the immune an central nervous systems, in which immune/pro-inflammatory mediators signal the hypothalamic-pituitary-adrenal axis to induce glucocorticoid-mediated restraint of the immune response. We have established the physiologic significance of this feedback loop in our studies in Lewis (LEW/N) rats, in which we have shown that susceptibility to inflammatory arthritis is related to a defect in the central component of this negative feedback loop, resulting in deficient CRH responses to challenge with a variety of inflammatory and stress mediators. We now extend these initial studies to show that the lEW/N CRH stress hyporesponsiveness, relateive to other strains, is profound, and extends across a variety of neurotransmitters and behavioral stressors. It appears as early in ontogeny as postnatal Day 14, and indicates that LEW/N rats fail to emerge from the stress-hyporesponsive period. It is associated with a variety of defined behavioral patterns, consistent with the differential HPA axis and neurotransmitter responsiveness of these two strains. Although several neurotransmitter systems do not differ in these strains (norepinephrine, 5HT2, acetylcholine), the benzodiazepine/GABA receptor complex, 5-HT1A system, and glucocorticoid Type 1 and Type 2 receptor systems differ in receptor number and/or ligand metabolism in these strains. The differences are organ and/or CNS site specific, and may be secondary to or play a causal role in the CRH hyporesponsiveness, and could contribute to or amplify some of the behavioral and/or inflammatory disease phenotypes in these strains. Thus, the lEW/N rat represents an example of a genetically based HPA axis hyporesponsiveness associated with susceptibility to inflammatory and behavioral disease.
| Thayer, Julian F; Verkuil, Bart; Brosschot, Jos F et al. (2010) Effects of the physical work environment on physiological measures of stress. Eur J Cardiovasc Prev Rehabil 17:431-9 |
| Butts, Cherie L; Bowers, Eve; Horn, J Cash et al. (2008) Inhibitory effects of progesterone differ in dendritic cells from female and male rodents. Gend Med 5:434-47 |
| Butts, Cherie L; Shukair, Shetha A; Duncan, Kristina M et al. (2007) Evaluation of steroid hormone receptor protein expression in intact cells using flow cytometry. Nucl Recept Signal 5:e007 |
| Tait, A Sasha; Dalton, Monique; Geny, Blandine et al. (2007) The large clostridial toxins from Clostridium sordellii and C. difficile repress glucocorticoid receptor activity. Infect Immun 75:3935-40 |
| Eskandari, Farideh; Martinez, Pedro E; Torvik, Sara et al. (2007) Low bone mass in premenopausal women with depression. Arch Intern Med 167:2329-36 |
| Marques, Andrea H; Cizza, Giovanni; Sternberg, Esther (2007) [Brain-immune interactions and implications in psychiatric disorders] Rev Bras Psiquiatr 29 Suppl 1:S27-32 |
| Sternberg, Esther M; Silverman, Marni N; Cizza, Giovanni (2007) The neuroendocrine system and rheumatoid arthritis: insights from anti-tumor necrosis factor-alpha therapy. J Rheumatol 34:1443-5 |
| Butts, C L; Shukair, S A; Duncan, K M et al. (2007) Effects of dexamethasone on rat dendritic cell function. Horm Metab Res 39:404-12 |
| Butts, Cherie L; Shukair, Shetha A; Duncan, Kristina M et al. (2007) Progesterone inhibits mature rat dendritic cells in a receptor-mediated fashion. Int Immunol 19:287-96 |
| Thayer, Julian F; Sternberg, Esther (2006) Beyond heart rate variability: vagal regulation of allostatic systems. Ann N Y Acad Sci 1088:361-72 |
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