Chronic intermittent psychosocial stress (social defeat/overcrowding) in mice increases the severity of an acute DSS-induced colitis and impairs regeneration.
Ulcerative colitis is a multifactorial disease, with immunological, genetic, and environmental factors playing an important role in its pathogenesis. Here we investigated the consequences of exposure to chronic psychosocial stress on the severity of a dextran sulfate sodium (DSS)-induced colitis in male C57BL/6 mice. Chronic stress was induced by repeated exposure to social defeat (SD, 2 h) and overcrowding (OC, 24 h) during 19 consecutive days. SD/OC mice showed a diminished body weight gain, thymus-atrophy, and adrenal hypertrophy, but similar light-phase plasma corticosterone concentrations, compared with unstressed mice. In contrast, the rise in dark-phase corticosterone concentration was significantly attenuated in SD/OC mice, whereas plasma ACTH concentrations and hypothalamic CRH mRNA expression did not differ between stressed and nonstressed groups. Additionally, adrenal cells from SD/OC mice showed a decreased in vitro response to ACTH stimulation. Subsequent treatment with 1% DSS for 7 d resulted in a more severe intestinal inflammation in SD/OC mice, as reflected by an increase in body weight loss, histological damage scores, and secretion of IL-6, TNFalpha, and interferon-gamma from mesenteric lymph node cells and by decreased colon length. The impaired health status of stressed mice was also reflected by a significantly lower survival rate after termination of the DSS treatment. In conclusion, the present findings demonstrate that chronic intermittent exposure to a psychosocial stressor before the induction of acute DSS-colitis results in adrenal insufficiency, increases in the severity of the acute inflammation, and impairs the healing phase.
Reber
S O
SO
Institute of Zoology, University of Regensburg, 93053 Regensburg, Germany.
Obermeier
F
F
Straub
R H
RH
Straub
H R
HR
Falk
W
W
Neumann
I D
ID
D000208:Acute Disease; D000311:Adrenal Glands / Q000033:anatomy & histology / Q000254:growth & development; D000324:Adrenocorticotropic Hormone / Q000097:blood; D000818:Animals; D003092:Colitis / Q000139:chemically induced* / Q000517:prevention & control*; D003345:Corticosterone / Q000097:blood; D003346:Corticotropin-Releasing Hormone / Q000378:metabolism; D003441:Crowding / Q000523:psychology*; D016207:Cytokines / Q000378:metabolism; D016264:Dextran Sulfate; D007030:Hypothalamo-Hypophyseal System / Q000502:physiology; D007031:Hypothalamus / Q000378:metabolism; D008198:Lymph Nodes / Q000502:physiology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D010913:Pituitary-Adrenal System / Q000502:physiology; D012333:RNA, Messenger / Q000096:biosynthesis; D012038:Regeneration / Q000502:physiology*; D012930:Social Dominance; D013315:Stress, Psychological / Q000503:physiopathology* / Q000523:psychology; D013950:Thymus Gland / Q000033:anatomy & histology / Q000254:growth & development
D016207:Cytokines; D012333:RNA, Messenger; D000324:Adrenocorticotropic Hormone; D003346:Corticotropin-Releasing Hormone; D016264:Dextran Sulfate; D003345:Corticosterone