Splenic glucocorticoid resistance following psychosocial stress requires physical injury.
Ontology highlight
ABSTRACT:
SUBMITTER: Foertsch S
PROVIDER: S-EPMC5691078 | biostudies-literature | 2017 Nov
REPOSITORIES: biostudies-literature
Publications
Splenic glucocorticoid resistance following psychosocial stress requires physical injury.
Foertsch Sandra S Füchsl Andrea M AM Faller Sandra D SD Hölzer Hannah H Langgartner Dominik D Messmann Joanna J Strauß Gudrun G Reber Stefan O SO
Scientific reports 20171116 1
Mice exposed to chronic subordinate colony housing (CSC) stress show glucocorticoid (GC) resistance of in vitro lipopolysaccharide (LPS)-stimulated splenocytes, increased anxiety and colitis. Similar effects were reported in wounded mice exposed to social disruption (SDR). Here we show that CSC exposure induced GC resistance in isolated and in vitro LPS-stimulated, but not unstimulated, splenocytes, and these effects were absent when CD11b<sup>+</sup> splenocytes were depleted. Moreover, re-acti ...[more]
Similar Datasets
Project description:Traumatic physical injury can result in many disabling sequelae including physical and mental health problems and impaired social functioning.To assess the effectiveness of psychosocial interventions in the prevention of physical, mental and social disability following traumatic physical injury.The search was not restricted by date, language or publication status. We searched the following electronic databases; Cochrane Injuries Group Specialised Register, CENTRAL (The Cochrane Library 2009, Issue 1), MEDLINE (Ovid SP), EMBASE (Ovid SP), PsycINFO (Ovid SP), Controlled Trials metaRegister (www.controlled-trials.com), AMED (Allied & Complementary Medicine), ISI Web of Science: Social Sciences Citation Index (SSCI), PubMed. We also screened the reference lists of all selected papers and contacted authors of relevant studies. The latest search for trials was in February 2008.Randomised controlled trials that consider one or more defined psychosocial interventions for the prevention of physical disability, mental health problems or reduced social functioning as a result of traumatic physical injury. We excluded studies that included patients with traumatic brain injury (TBI).Two authors independently screened the titles and abstracts of search results, reviewed the full text of potentially relevant studies, independently assessed the risk of bias and extracted data.We included five studies, involving 756 participants. Three studies assessed the effect of brief psychological therapies, one assessed the impact of a self-help booklet, and one the effect of collaborative care. The disparate nature of the trials covering different patient populations, interventions and outcomes meant that it was not possible to pool data meaningfully across studies. There was no evidence of a protective effect of brief psychological therapy or educational booklets on preventing disability. There was evidence from one trial of a reduction in both post-traumatic stress disorder (PTSD) and depressive symptoms one month after injury in those who received a collaborative care intervention combined with a brief psycho-educational intervention, however this was not retained at follow up. Overall mental health status was the only disability outcome affected by any intervention. In three trials the psychosocial intervention had a detrimental effect on the mental health status of patients.This review provides no convincing evidence of the effectiveness of psychosocial interventions for the prevention of disability following traumatic physical injury. Taken together, our findings cannot be considered as supporting the provision of psychosocial interventions to prevent aspects of disability arising from physical injury. However, these conclusions are based on a small number of disparate trials with small to moderate sample sizes and are therefore necessarily cautious. More research, using larger sample sizes, and similar interventions and patient populations to enable pooling of results, is needed before these findings can be confirmed.
| S-EPMC3428876 | biostudies-other
Project description:Acute and chronic stress are important factors in the development of mental disorders. Reliable measurement of stress reactivity is therefore pivotal. Critically, experimental induction of stress often involves multiple "hits" and it is an open question whether individual differences in responses to an earlier stressor lead to habituation, sensitization, or simple additive effects on following events. Here, we investigated the effect of the individual cortisol response to intravenous catheter placement (IVP) on subsequent neural, psychological, endocrine, and autonomous stress reactivity. We used an established psychosocial stress paradigm to measure the acute stress response (Stress) and recovery (PostStress) in 65 participants. Higher IVP-induced cortisol responses were associated with lower pulse rate increases during stress recovery (b = -4.8 bpm, p = .0008) and lower increases in negative affect after the task (b = -4.2, p = .040). While the cortisol response to IVP was not associated with subsequent specific stress-induced neural activation patterns, the similarity of brain responses Pre- and PostStress was higher IVP-cortisol responders (t[64] = 2.35, p = .022) indicating faster recovery. In conclusion, preparatory stress induced by IVP reduced reactivity in a subsequent stress task by modulating the latency of stress recovery. Thus, an individually stronger preceding release of cortisol may attenuate a second physiological response and perceived stress suggesting that relative changes, not absolute levels are crucial for stress attribution. Our study highlights that considering the entire trajectory of stress induction during an experiment is important to develop reliable individual biomarkers.
| S-EPMC7469805 | biostudies-literature
Project description:The subgranular zone of the adult hippocampal dentate gyrus contains a pool of neural stem cells that continuously divide and differentiate into functional granule cells. It has been shown that production of new hippocampal neurons is necessary for amelioration of stress-induced behavioral changes by antidepressants in animal models of depression. The survival of newly born hippocampal neurons is decreased by chronic psychosocial stress and increased by exposure to enriched environments. These observations suggest the existence of a link between hippocampal neurogenesis, stress-induced behavioral changes, and the beneficial effects of enriched environment. To show causality, we subjected transgenic mice with conditionally suppressed neurogenesis to psychosocial stress followed by environmental enrichment. First, we showed that repeated social defeat coupled with chronic exposure to an aggressor produces robust and quantifiable indices of submissive and depressive-like behaviors; second, subsequent exposure to an enriched environment led to extinction of the submissive phenotype, while animals exposed to an impoverished environment retained the submissive phenotype; and third, enrichment was not effective in reversing the submissive and depressive-like behaviors in transgenic mice lacking neurogenesis. Our data show two main findings. First, living in an enriched environment is highly effective in extinguishing submissive behavioral traits developed during chronic social stress, and second, these effects are critically dependent on adult neurogenesis, indicating that beneficial behavioral adaptations are dependent on intact adult neurogenesis.
| S-EPMC2990187 | biostudies-literature
Project description:The understanding of mechanisms linking psychological stress to disease risk depend on reliable stress biomarkers. Circulating cell-free DNA (cfDNA) has emerged as a potential biomarker of cellular stress, aging, inflammatory processes, and cell death. Recent studies indicated that psychosocial stress and physical exercise might also influence its release. We compared the effects of acute psychosocial and physical exercise stress on cfDNA release by exposing 20 young, healthy men to both an acute psychosocial laboratory stressor and an acute physical exercise stressor. Venous blood and saliva samples were collected before and after stress exposure. Cell-free DNA was extracted from plasma and quantified by qPCR. Furthermore, cfDNA fragment length was analyzed and cfDNA methylation patterns were assayed across time. In addition, release of stress hormones and subjective stress responses were measured. Results showed a twofold increase of cfDNA after TSST and fivefold increase after exhaustive treadmill exercise, with an overabundance of shorter cfDNA fragments after physical exhaustion. Interestingly, cell-free mitochondrial DNA showed similar increase after both stress paradigms. Furthermore, cfDNA methylation signatures-used here as a marker for diverse cellular origin-were significantly different post stress tests. While DNA methylation decreased immediately after psychosocial stress, it increased after physical stress, suggesting different cellular sources of active DNA release. In summary, our results suggest stimulus and cell-specific regulation of cfDNA release. Whereas the functional role of stress-associated cfDNA release remains elusive, it might serve as a valuable biomarker in molecular stress research as a part of the psychophysiological stress response.
| S-EPMC6206142 | biostudies-literature
Project description:The goal of this study was to compare transcriptional profiles of the amygdala from control and (PS) prenatally stressed male and female offspring to elucidate sex-specific molecular mechanisms underlying behavioral and neuroendocrine abnormalities observed after in-utero psychosocial stress exposure. Amygdalar mRNA profiles of 28 day old control and PS male and female mice were generated by preparing sequencing libraries using the NEBNext Ultr II Directional RNA Library Prep Kit for Illumina. After indexing, enrichment through 8 cycles of PCR, and passing initial quality control metrics, individually indexed and compatible libraries were proportionally pooled and sequenced using Nextseq 550 sequencer. The sequencing setting of single read 1 × 85 bp to generate ∼50 M reads per sample was used. Differentially expressed genes (DEGs) were analyzed using RUVseq and EdgeR. Results were validated via qPCR We find psychosocial PS results in the emergence of anxiety-like behaviors, an altered behavioral coping strategy to stress, and anhedonia in male and female offspring. Neuroendocrine abnormalities, evidenced by acute stress-induced HPA axis hyperactivity, are only observed in PS female offspring. Our RNA-seq analysis reveals these phenotypic changes in PS offspring to be associated with sex-specific disturbances in genes associated with synaptic transmission, including genes associated with glutamatergic and GABAergic signaling in PS males, and upregulation of DBH, known to regulate NE synthesis, in PS females. Our study represents one of the first detailed analysis of amygdalar transcriptomes generated by RNA-seq comparing control vs prenatally stressed offspring, identifying sex-specific changes in response to in-utero psychosocial stress exposure.
2022-02-08 | GSE189330 | GEO
Project description:During alveolar repair, alveolar type 2 (AT2) epithelial cell progenitors rapidly proliferate and differentiate into flat AT1 epithelial cells. Failure of normal alveolar repair mechanisms can lead to loss of alveolar structure (emphysema) or development of fibrosis, depending on the type and severity of injury. To test if β1-containing integrins are required during repair following acute injury, we administered E. coli lipopolysaccharide (LPS) by intratracheal injection to mice with a postdevelopmental deletion of β1 integrin in AT2 cells. While control mice recovered from LPS injury without structural abnormalities, β1-deficient mice had more severe inflammation and developed emphysema. In addition, recovering alveoli were repopulated with an abundance of rounded epithelial cells coexpressing AT2 epithelial, AT1 epithelial, and mixed intermediate cell state markers, with few mature type 1 cells. AT2 cells deficient in β1 showed persistently increased proliferation after injury, which was blocked by inhibiting NF-κB activation in these cells. Lineage tracing experiments revealed that β1-deficient AT2 cells failed to differentiate into mature AT1 epithelial cells. Together, these findings demonstrate that functional alveolar repair after injury with terminal alveolar epithelial differentiation requires β1-containing integrins.
| S-EPMC10443799 | biostudies-literature
Project description:We propose a model wherein chronic stress results in glucocorticoid receptor resistance (GCR) that, in turn, results in failure to down-regulate inflammatory response. Here we test the model in two viral-challenge studies. In study 1, we assessed stressful life events, GCR, and control variables including baseline antibody to the challenge virus, age, body mass index (BMI), season, race, sex, education, and virus type in 276 healthy adult volunteers. The volunteers were subsequently quarantined, exposed to one of two rhinoviruses, and followed for 5 d with nasal washes for viral isolation and assessment of signs/symptoms of a common cold. In study 2, we assessed the same control variables and GCR in 79 subjects who were subsequently exposed to a rhinovirus and monitored at baseline and for 5 d after viral challenge for the production of local (in nasal secretions) proinflammatory cytokines (IL-1β, TNF-α, and IL-6). Study 1: After covarying the control variables, those with recent exposure to a long-term threatening stressful experience demonstrated GCR; and those with GCR were at higher risk of subsequently developing a cold. Study 2: With the same controls used in study 1, greater GCR predicted the production of more local proinflammatory cytokines among infected subjects. These data provide support for a model suggesting that prolonged stressors result in GCR, which, in turn, interferes with appropriate regulation of inflammation. Because inflammation plays an important role in the onset and progression of a wide range of diseases, this model may have broad implications for understanding the role of stress in health.
| S-EPMC3341031 | biostudies-other
Project description:Traumatic brain injury (TBI) is associated with increased risk for mental health disorders, impacting post-injury quality of life and societal reintegration. TBI is also associated with deficits in psychosocial processing, defined as the cognitive integration of social and emotional behaviors, however little is known about how these deficits manifest and their contributions to post-TBI mental health. In this pre-clinical investigation using rats, a single mild blast TBI (mbTBI) induced impairment of psychosocial processing in the absence of confounding physical polytrauma, post-injury motor deficits, affective abnormalities, or deficits in non-social behavior. Impairment severity correlated with acute upregulations of a known oxidative stress metabolite, 3-hydroxypropylmercapturic acid (3-HPMA), in urine. Resting state fMRI alterations in the acute post-injury period implicated key brain regions known to regulate psychosocial behavior, including orbitofrontal cortex (OFC), which is congruent with our previous report of elevated acrolein, a marker of neurotrauma and 3-HPMA precursor, in this region following mbTBI. OFC of mbTBI-exposed rats demonstrated elevated mRNA expression of metabotropic glutamate receptors 1 and 5 (mGluR1/5) and injection of mGluR1/5-selective agonist in OFC of uninjured rats approximated mbTBI-induced psychosocial processing impairment, demonstrating a novel role for OFC in this psychosocial behavior. Furthermore, OFC may serve as a hotspot for TBI-induced disruption of psychosocial processing and subsequent mental health disorders.
| S-EPMC9284795 | biostudies-literature
Project description:Brain serotonin (5-HT) deficiency and exposure to psychosocial stress have both been implicated in the etiology of depression and anxiety disorders, but whether 5-HT deficiency influences susceptibility to depression- and anxiety-like phenotypes induced by psychosocial stress has not been formally established. Most clinically effective antidepressants increase the extracellular levels of 5-HT, and thus it has been hypothesized that antidepressant responses result from the reversal of endogenous 5-HT deficiency, but this hypothesis remains highly controversial. Here we evaluated the impact of brain 5-HT deficiency on stress susceptibility and antidepressant-like responses using tryptophan hydroxylase 2 knockin (Tph2KI) mice, which display 60-80% reductions in brain 5-HT. Our results demonstrate that 5-HT deficiency leads to increased susceptibility to social defeat stress (SDS), a model of psychosocial stress, and prevents the fluoxetine (FLX)-induced reversal of SDS-induced social avoidance, suggesting that 5-HT deficiency may impair antidepressant responses. In light of recent clinical and preclinical studies highlighting the potential of inhibiting the lateral habenula (LHb) to achieve antidepressant and antidepressant-like responses, we also examined whether LHb inhibition could achieve antidepressant-like responses in FLX-insensitive Tph2KI mice subjected to SDS. Our data reveal that using designer receptors exclusively activated by designer drugs (DREADDs) to inhibit LHb activity leads to reduced SDS-induced social avoidance behavior in both WT and Tph2KI mice. This observation provides additional preclinical evidence that inhibiting the LHb might represent a promising alternative therapeutic approach under conditions in which selective 5-HT reuptake inhibitors are ineffective.
| S-EPMC4345581 | biostudies-literature
Project description:BackgroundSplenic injury due to colonoscopy is rare, but has high mortality. While historically treated conservatively for low-grade injuries or with splenectomy for high-grade injuries, splenic artery embolisation is increasingly utilised, reflecting modern treatment guidelines for external blunt trauma. This systematic review evaluates outcomes of published cases of splenic injury due to colonoscopy treated with splenic artery embolisation.MethodsA systematic review was performed of published articles concerning splenic injury during colonoscopy treated primarily with splenic artery embolisation, splenectomy, or splenorrhaphy from 1977 to 2022. Datapoints included demographics, past surgical history, indication for colonoscopy, delay to diagnosis, treatment, grade of injury, splenic artery embolisation location, splenic preservation (salvage), and mortality.ResultsThe 30 patients treated with splenic artery embolisation were of mean age 65 (SD 9) years and 67% female, with 83% avoiding splenectomy and 6.7% mortality. Splenic artery embolisation was proximal to the splenic hilum in 81%. The 163 patients treated with splenectomy were of mean age 65 (SD 11) years and 66% female, with 5.5% mortality. Three patients treated with splenorrhaphy of median age 60 (range 59-70) years all avoided splenectomy with no mortality. There was no difference in mortality between splenic artery embolisation and splenectomy cohorts (p = 0.81).ConclusionsSplenic artery embolisation is an effective treatment option in splenic injury due to colonoscopy. Given the known benefits of splenic salvage compared to splenectomy, including preserved immune function against encapsulated organisms, low cost, and shorter hospital length of stay, embolisation should be incorporated into treatment pathways for splenic injury due to colonoscopy in suitable patients.
| S-EPMC10859723 | biostudies-literature