Aggravation of DSS-induced colitis after chronic subordinate colony (CSC) housing is partially mediated by adrenal mechanisms

Chronic subordinate colony housing (CSC) is a relevant chronic psycho-social stressor for male mice. Here, we investigated effects of CSC on the severity of dextran sulphate sodium (DSS)-induced colitis and the involvement of adrenal mechanisms. After 19 days of CSC, male C57BL/6 mice were treated with 1% DSS (8 days). After 8 days, inflammatory shortening of the colon and the histological inflammation score were increased in CSC mice. Additionally, the increased secretion of pro-inflammatory cytokines by mesenteric lymph node cells found on day 2 and 4 of DSS treatment was down-regulated in CSC mice on day 8 of DSS treatment, paralleled by an increase in plasma corticosterone. In contrast, in unstressed controls, elevation of cytokine secretion was delayed and only found on day 8 of DSS treatment, associated with a prompt rise in plasma corticosterone. To reveal adrenal mechanisms in CSC-induced effects on colitis, mice were adrenalectomized, exposed to CSC and treated with DSS (8 days). In adrenalectomized CSC mice, the severity of DSS-induced colitis was reduced, as body weight loss, shortening of colon, histological damage score, and cytokine secretion from mesenteric lymph node cells were diminished compared with sham-operated CSC mice. In conclusion, exposure to chronic psycho-social stress increases the severity of acute DSS colitis, an effect which is, at least partly, mediated by adrenal mechanisms.     

Chronic psychosocial stress increases the risk for inflammation-related colon carcinogenesis in male mice

Patients with inflammatory bowel diseases (IBDs) have a higher risk of developing colorectal cancer (CRC) than the general population. Furthermore, chronic psychosocial stress increases the likelihood of developing IBD and multiple types of malignant neoplasms, including CRC. Here, for the first time, we investigate the effects of chronic psychosocial stress in male mice on an artificially induced CRC, by employing the chronic subordinate colony (CSC) housing paradigm in combination with the reliable azoxymethane (AOM)/dextran sodium sulfate (DSS) CRC model. Colonoscopy revealed that CSC mice showed accelerated macroscopic suspect lesions. In addition, more CSC mice developed low-grade dysplasia (LGD) and/or high-grade dysplasia (HGD) in the colonic tissue compared to the single-housed control mice (SHC). CSC mice showed an increased number of Ki67+ and a decreased number of terminal deoxynucleotidyl transferase dUTP nick end labeling epithelial cells in colonic tissue. Colonic liver receptor homolog-1 (LRH-1), cyclooxygenase II (COXII), tumor necrosis factor, forkhead box P3 (FoxP3) mRNA as well as colonic ?-catenin, COXII, and LRH-1 protein expression were also increased in CSC compared with SHC mice. Although the number of CD4+ Th cells was increased, a tendency toward a decreased colonic interferon-γ (IFN-γ) mRNA expression was observed. Furthermore, despite an increased percentage of CD3+ cells and CD3+/FoxP3+ double-positive cells within mesenteric lymph node cells of CSC mice, IFN-γ secretion from these cells was unaffected. Altogether, our results suggest that chronic psychosocial stress increases the risk for AOM/DSS-induced and, thus, inflammation-related CRC. Finally, assessment of additional time points may test whether the shift from tumor-protective Th1 cell to regulatory T-cell immunity represents a consequence of increased carcinogenesis or a causal factor involved in its development.     

Effects of repetitive stress during the acute phase of Trypanosoma cruzi infection on chronic Chagas' disease in rats

The effect of repetitive stress during acute infection with Trypanosoma cruzi (T. cruzi) on the chronic phase of ensuing Chagas' disease was the focus of this investigation. The aim of this study was to evaluate in Wistar rats the influence of repetitive stress during the acute phase of infection (7 days) with the Y strain of T. cruzi on the chronic phase of the infection (at 180 days). Exposure to ether vapor for 1 min twice a day was used as a stressor. Repetitive stress enhanced the number of circulating parasites and cardiac tissue disorganization, from a moderate to a severe diffuse mononuclear inflammatory process and the presence of amastigote burden in the cardiac fibers. Immunological parameters revealed that repetitive stress triggered a reduced concanavalin A induced splenocyte proliferation in vitro with major effects on the late chronic phase. Serum interleukin-12 concentration decreased in both stressed and infected rats in the early phase of infection although it was higher on 180 days post-infection. These results suggest that repetitive stress can markedly impair the host's immune system and enhance the pathological process during the chronic phase of Chagas' disease.     

An Acute Stressor Enhances Sensitivity to a Chemical Irritant and Increases 51CrEDTA Permeability of the Colon in Adult Rats

We investigated the effect of prior acute stress on colonic permeability induced by a chemical irritant known to induce symptoms similar to inflammatory bowel disease in rodents. Adult male rats (n = 12) were stressed by a single session of ten unpredictable, uncontrollable foot shocks, and half were home cage controls (n = 12). Twenty-nine days later, half of each treatment group was exposed to 4% DSS (dextran sulphate sodium) solution in their drinking water for 48 hours while half received pure water over two periods separated by 17 days. After food deprivation overnight and light isoflurane anaesthesia the following morning, the animals were given a colonic infusion of 2000 nCi (nanocurie) 51CrEDTA (51Cr-labelled ethylenediaminetetraacetic acid) and then placed individually in metabolic cages for a six hours continuous urine collection. Radioactivity in urine was measured by a gamma counter and percentage recovery of 51CrEDTA calculated as an indicator of colonic mucosal permeability. Results concluded that pre-shocked animals exposed to DSS showed significantly higher mucosal permeability than the pre-shocked animals given water, and the non-shocked animals given either DSS or water. Pre-shock in combination with two exposures to a chemical irritant separated by 17 days had a pronounced effect on colonic permeability, indicating that stress should be considered a possible initiating or contributory factor to increased intestinal permeability related to a mucosal challenge.     

An acute stressor enhances sensitivity to a chemical irritant and increases51CrEDTA permeability of the colon in adult rats

We investigated the effect of prior acute stress on colonic permeability induced by a chemical irritant known to induce symptoms similar to inflammatory bowel disease in rodents. Adult male rats (n=12) were stressed by a single session of ten unpredictable, uncontrollable foot shocks, and half were home cage controls (n=12). Twenty-nine days later, half of each treatment group was exposed to 4% DSS (dextran sulphate sodium) solution in their drinking water for 48 hours while half received pure water over two periods separated by 17 days. After food deprivation overnight and light isoflurane anaesthesia the following morning, the animals were given a colonic infusion of 2000 nCi (nanocurie)⁵¹CrEDTA (⁵¹Cr-labelled ethylenediaminetetraacetic acid) and then placed individually in metabolic cages for a six hours continuous urine collection. Radioactivity in urine was measured by a gamma counter and percentage recovery of⁵¹CrEDTA calculated as an indicator of colonic mucosal permeability. Results concluded that pre-shocked animals exposed to DSS showed significantly higher mucosal permeability than the pre-shocked animals given water, and the non-shocked animals given either DSS or water. Pre-shock in combination with two exposures to a chemical irritant separated by 17 days had a pronounced effect on colonic permeability, indicating that stress should be considered a possible initiating or contributory factor to increased intestinal permeability related to a mucosal challenge.     

Combined effect of early life stress and acute stress on colonic sensory and motor responses through serotonin pathways: differences between proximal and distal colon in rats

Clinically, adults who have experienced stresses in childhood present with episodes of serious symptoms of irritable bowel syndrome that are associated with acute stress, but the mechanism is not well understood. This study aimed to investigate the colonic sensory/motor responses to acute water avoidance stress (WAS) in male adult rats subjected to neonatal maternal separation (NMS), and the underlying mechanism of sensory/motor responses. Effects of the combined acute and early life stress on visceral sensation, colonic motility, and the tissue and luminal content of serotonin (5-hydroxytryptamine, 5-HT) in the proximal and distal colon were evaluated using the abdominal withdrawal reflex test, faecal pellet output measurement and capillary electrophoresis analysis, respectively. Results showed that WAS significantly increased not only visceral sensitivity but also colonic motility in NMS rats compared to the normal rats. These alterations were accompanied by significant increase in 5-HT content in the proximal but not the distal colonic tissues; these alterations were also associated with increased density of enterochromaffin (EC) cells in the proximal segment. In contrast, the faecal content of 5-HT increased similarly in both segments. Consecutive administration of parachlorophenylalanine to NMS rats was more potent at 500 mg kg?1 day?1 than at 150 mg kg?1 day?1 in suppressing colonic sensory/motor responses to WAS, corresponding to the greater reduction of the tissue and faecal content of 5-HT and of EC cell density in the colon. These data indicate that combined early life stress and acute stress effectively induce visceral hyperalgesia and motility disorder through 5-HT pathways in the colon of rats, and the proximal and distal colon have different responses towards the combined stressors.     

The Complexity and Challenges of Genetic Counseling and Testing for Inflammatory Bowel Disease

Inflammatory bowel disease (IBD) is an umbrella term referring to two chronic idiopathic intestinal diseases: ulcerative colitis (UC) and Crohn’s disease (CD). Both UC and CD are characterized by immune activation that leads to symptoms, but the location, severity and behavior of the inflammation varies among individuals and in characteristic ways between UC and CD. A majority of patients with IBD are diagnosed in young adulthood, but the response to therapy is variable and difficult to predict, with some patients demonstrating a prompt and effective remission while others have continuous symptoms that do not respond to existing medical options. Surgery remains a frequent and necessary occurrence among patients with IBD, but in UC it is considered curative, while in CD only temporizing. Clinical observations, epidemiological studies, and molecular genetics have provided strong evidence that both genetic and environmental factors are important determinants for disease susceptibility. In recent years, a number of genes have been identified that associate with CD and UC, although the clinical utility of these discoveries in patients or in susceptible family members has not been determined. Nonetheless, it is hoped that these fundamental advances in our understanding of IBD will lead to better therapies for patients and prevention strategies for those who are susceptible. Effective incorporation of clinical genetic testing for IBD into practice will require appropriate education and counseling.     

Chronic stress modulates the use of spatial and stimulus-response learning strategies in mice and man

Acute stress modulates multiple memory systems in favor of caudate nucleus-dependent stimulus-response and at the expense of hippocampus-dependent spatial learning and memory. We examined in mice and humans whether chronic stress has similar consequences. Male C57BL/6J mice that had been repeatedly exposed to rats ("rat stress") used in a circular hole board task significantly more often a stimulus-response strategy (33%) than control mice (0%). While velocity was increased, differences in latency to exit hole, distance moved or number of holes visited were not observed. Increased velocity and performance during retention trials one day later indicates altered emotionality and motivation to explore in rat stressed mice. Forty healthy young men and women were split into "high chronic stress" and "low chronic stress" groups based on their answers in a chronic stress questionnaire ("Trier Inventory of Chronic Stress"-TICS) and trained in a 2D task. A test trial immediately after training revealed that participants of the "high chronic stress" group used the S-R strategy significantly more often (94%) than participants of the "low chronic stress" group (52%). Verbal self-reports confirmed the strategy derived from participants' choice in the test trial. Learning performance was unaffected by the chronic stress level. We conclude that one consequence of chronic stress is the shift to more rigid stimulus-response learning, that is accompanied by changes in motivational factors in mice.     

A study of the effets of restraint stress on colitis induced by dextran sulphate sodium in singly housed rats

The inflammatory bowel diseases (Crohn’s disease and ulcerative colitis) are multifactorial diseases. Clinical reports indicate that emotional stress may contribute to the onset, progression and remission of these diseases. Using an experimental animal model of ulcerative colitis, the effect of stress on the development of and recovery from symptoms, was studied prospectively. Singly housed rats received 4 percent dextran sulphate sodium orally until, fecal blood was detected, indicating the presence of colonic erosions. Tap water was then administered until there were no signs of fecal blood. Two hours of restraint stress were administered daily over four successive days, either prior to or after the induction of colitis. Latencies in days to symptom development and recovery were compared to an unstressed, group. Daily measures of fluid-intake, body-weight, and hemoglobulin in feces were made. Results  Rats exposed to restraint stress procedures prior to induction of colitis had shorter latencies to development of symptoms. There was no significant difference in latency to recovery. The amount of fluid-intake did not significantly differ between groups, nor did the groups differ in body-weight. Conclusion  There is an effect of stress on the latency to develop colitis induced by dextran sulphate sodium. This preliminary study suggests that the impact of stress may be one factor underlying the emergence of ulcerative colitis.     

Evaluation of a psychological treatment for inflammatory bowel disease

Inflammatory bowel disease (IBD) encompasses two related gastrointestinal-tract diseases, ulcerative colitis (UC) and Crohn's Disease (CD). This study, a randomized controlled trial, compared the effectiveness of a multi-component behavioral treatment package (n = 11), which included IBD education, progressive muscle relaxation, thermal biofeedback, and training in use of cognitive coping strategies, to the effectiveness of symptom-monitoring (n = 10) as a control condition; 8 controls subsequently completed treatment. At posttreatment, the treatment group showed mean reductions on 5 symptoms, while the symptom monitoring controls showed mean reductions on all 8 symptoms. On a measure of Total Symptomatic change, the controls showed more improvement than the treated group; the treated controls at posttreatment, showed increases on all 8 symptoms. However, treated subjects perceived themselves as coping better with IBD, as feeling less IBD-related stress, and as experiencing less depression and anxiety. It is hypothesized that inherent differences may have existed between CD and UC subjects which could have led to the differences seen in treatment responses.     

Hypothalamic circuit regulating colonic transit following chronic stress in rats

Although acute stress accelerates colonic transit, the effect of chronic stress on colonic transit remains unclear. In this study, rats received repeated restraint stress (chronic homotypic stress) or various types of stress (chronic heterotypic stress) for 5 and 7 days, respectively. Vehicle saline, oxytocin (OXT), OXT receptor antagonist or corticotropin-releasing factor (CRF) receptor antagonists were administered by intracerebroventricular (ICV) injection prior to restraint stress for 90 min. Immediately after the stress exposure, the entire colon was removed and the geometric center (GC) of Na51CrO4 (a nonabsorbable radioactive marker; 0.5 μCi) distribution was calculated to measure the transit. Gene expression of OXT and CRF in the paraventricular nucleus (PVN) was evaluated by in situ hybridization. Accelerated colonic transit with the acute stressor was no longer observed following chronic homotypic stress. This restored colonic transit was reversed by ICV injection of an OXT antagonist. In contrast, chronic heterotypic stress significantly accelerated colonic transit, which was attenuated by ICV injection of OXT and by a CRF receptor 1 antagonist. OXT mRNA expression in the PVN was significantly increased following chronic homotypic stress, but not chronic heterotypic stress. However, CRF mRNA expression in the PVN was significantly increased following acute and chronic heterotypic stress, but not chronic homotypic stress. These results indicate that central OXT and CRF play a pivotal role in mediating the colonic dysmotility following chronic stress in rats.     

Relation of Repetitive Thinking Styles with Anxiety and Depression in Patients with Inflammatory Bowel Disease

In this study, we aimed to evaluate the relationship between the repetitive thinking styles and anxiety and depression in patients with inflammatory bowel disease (IBD). One hundred IBD outpatients (39 active and 61 remission) attending the gastroenterology clinic and 100 healthy controls were included.The rumination and worry scores of IBD patients, particularly in their active period, were significantly higher than controls. Additionally, the correlation of rumination and worry with anxiety and depression was statistically significant. Our results suggest that psychological interventions targeting repetitive thinking would alleviate depression and anxiety as well as GI symptoms in people with IBD which should be confirmed by further studies.

     

Chronic stress prior to hippocampal stroke enhances post-stroke spatial deficits in the ziggurat task

Stress is one of the most important variables to determine recovery following stroke. We have previously reported that post-stroke exposure to either stress or corticosterone (CORT) alleviates hippocampal ischemic outcome. The present experiment expands previous findings by investigating the influence of exposure to stress prior to ischemic event. Rats received either daily restraint stress (1h/day; 16 consecutive days) or CORT (0.5mg/kg; 16 consecutive days) prior to focal ischemic stroke in the hippocampus induced by bilateral injection of endothelin-1 (ET-1). All experimental groups were then tested in the ziggurat task, a new task for spatial cognition. The stress+stroke group showed significant deficits in both hippocampal structure and function. No deleterious effect of pre-stroke exposure to CORT was found in the CORT+stroke group. Our results indicate that a history of chronic stress sensitizes hippocampal cells to the damaging consequences of focal ischemia. The opposing effects of CORT-related experiences in this study not only reflect the diversity of glucocorticoid actions in the stress response, but also provide evidence that elevated CORT in the absence of emotional disturbance is not sufficient to produce hippocampal deficit.     

从炎症在心力衰竭进展中的作用谈心力衰竭治疗策略的制订

心力衰竭是一个以免疫激活和低程度的慢性炎症为特点的疾病。一些炎症因子能通过促进心肌细胞肥厚、恶化心肌收缩功能以及诱导凋亡,在心衰的发展过程中具有重要作用。炎症因子能成为心衰治疗的重要目标。但炎症因子还有心脏代偿和保护作用。制订新的心衰治疗策略时需要进一步了解心衰中炎症反应激活的机制。     

Behavioral interventions may prolong remission in patients with inflammatory bowel disease

Inflammatory Bowel Diseases (IBDs) are chronic, relapsing and remitting gastrointestinal conditions with no known cure. Previous studies have linked behavioral factors, including stress and medication adherence, to relapse.

Purpose

We sought to determine the effect of participation in a behavioral self-management program on incidence of flare within 12 months following behavioral intervention when compared to the natural history of flare incidence prior to program participation.

Results

Results from a 2-level regression model indicated that those participants in the treatment group were 57% less likely to flare in the following 12 months (compared to 18% in the control group). The decline in “flare odds” was about 2 times greater in treatment versus controls (OR = 0.52, t(34) = 2.07, p < 0.05). Office visits, ER visits, and disease severity (all p < 0.05) were identified as moderators of flare risk.

Conclusions

We have demonstrated 1) a statistical model estimating the likelihood of flare rates in the 12 months following a behavioral intervention for IBD (compared to a control condition), and 2) that the introduction of a behavioral intervention can alter the natural course of a chronic, relapsing and remitting gastrointestinal condition such as IBD.     

Ileal inducible nitric oxide synthase mRNA expression in response to stress is modified in Sprague-Dawley rats exposed to a previous intestinal inflammation

The ability of stress to initiate or reactivate an inflammatory process seems to depend on an individual's susceptibility to stressful stimuli. The aim of this study was to establish whether previous inflammation alters the response to stress in Sprague-Dawley rats, a strain not especially susceptible to stressful stimuli. Stress exposure was performed in rats treated with indomethacin, to induce cyclic intestinal inflammation, during the inactive phase of inflammation. Both control and indomethacin-treated rats submitted to stress showed a decrease in body weight gain and blood leukocyte levels, as well as an increase in fecal pellet output. The increase in intestinal mucosal mast cell count induced by stress was similar in both groups of animals. Moreover, no differences were observed between control and indomethacin-treated rats in the degree of bacterial translocation and myeloperoxidase levels after stress exposure. Despite these similarities, differences between groups were observed in inducible nitric oxide synthase (iNOS) mRNA expression. Although ileal iNOS mRNA expression was inhibited in healthy rats submitted to stress, stress failed to modify this parameter in indomethacin-treated rats. As iNOS is another inflammatory marker, our results may allow the possibility that a previous intestinal inflammation could change the intestinal susceptibility to stress. Whether these differences in ileal iNOS expression can be indicative of a possible change in the predisposition to develop an intestinal inflammatory reaction in response to stress in Sprague-Dawley rats remains to be elucidated.     

The psychobiology of trait shame in young women: extending the social self preservation theory

OBJECTIVE: The social self preservation theory (SSPT) proposes that social evaluative threat evokes the emotion of shame, which then shapes a coordinated psychobiological response. While this is supported in acute stress studies, there is no data on chronic experiences of shame. DESIGN: We investigated the association of trait shame with activity of the hypothalamic-pituitary-adrenal (HPA) axis, of the sympathetic nervous system (SNS), and regulation of inflammation in n = 56 young women. MAIN OUTCOME MEASURES: Daily profiles of salivary cortisol and alpha-amylase were assessed as indices of HPA axis and SNS activity, respectively. Inflammatory regulation was assessed by lipopolysaccharide-stimulated production and glucocorticoid inhibition of interleukin-6 in vitro. RESULTS: Trait shame was associated with SNS (r = .49; p = .001), but not HPA activity (r = .14; ns). Shame was associated with inflammatory activity (r = .35; p = .006) and glucocorticoid sensitivity (r = -0.43; p = .001). Relationships were not mediated by HPA and SNS activity. CONCLUSIONS: Results support SSPT predictions with respect to chronic shame experience and inflammation. Results further suggest the importance of SNS activation related to shame, and the possibility that HPA activation may be limited acute experiences of shame.     

Life events stress and chronic pain

Stress in life has been found to play a role in triggering, maintaining and exacerbating chronic pain, yet, direct empirical evidence of the mechanism of such a role is limited. In the present study 120 non-selected chronic pain patients and an equal number of matched healthy normals were investigated with regard to life events stress. The investigation revealed that although, patients and controls did not differ in terms of number of events experienced during the last 1 year, however, patients reported significantly higher frequency of occurrence on a distinctive set of events belonging to personal, interpersonal and familial life and events related to change in eating and sleeping habits. Our results emphasize the importance of studying the life events beyond the simple count of number of event occurrence but to explore the specific events those cluster around pain disorders.     

A Study of the Effects of Restraint Stress on Colitis Induced by Dextran Sulphate Sodium in Singly Housed Rats

The inflammatory bowel diseases (Crohn's disease and ulcerative colitis) are multifactorial diseases. Clinical reports indicate that emotional stress may contribute to the onset, progression and remission of these diseases. Using an experimental animal model of ulcerative colitis, the effect of stress on the development of and recovery from symptoms was studied prospectively. Singly housed rats received 4 percent dextran sulphate sodium orally until fecal blood was detected, indicating the presence of colonic erosions. Tap water was then administered until there were no signs of fecal blood. Two hours of restraint stress were administered daily over four successive days, either prior to or after the induction of colitis. Latencies in days to symptom development and recovery were compared to an unstressed group. Daily measures of fluid-intake, body-weight, and hemoglobulin in feces were made. RESULTS: Rats exposed to restraint stress procedures prior to induction of colitis had shorter latencies to development of symptoms. There was no significant difference in latency to recovery. The amount of fluid-intake did not significantly differ between groups, nor did the groups differ in body-weight. CONCLUSION: There is an effect of stress on the latency to develop colitis induced by dextran sulphate sodium. This preliminary study suggests that the impact of stress may be one factor underlying the emergence of ulcerative colitis.