Effects Of Chronic Psychological Stress Research Articles

Changes in Anxiety-Related Behaviors, Voiding Patterns, and Urinary Bladder Contractile Properties in Male Mice Exposed to Water Avoidance Stress for 1 Day and 28 Days.

Repeated water avoidance stress (WAS) for 10 days is a common rodent model to mimic the effect of chronic psychological stress on urinary bladder dysfunction. However, it remains obscure whether changes in the stress exposure period impact urinary bladder impairment differently. Therefore, this study aimed to investigate the effect of 1 (acute), 10 (chronic), and 28 (prolonged) days of WAS on anxiety-related behavior, voiding pattern, urinary bladder mast cells, and bladder contractility in C57BL/6J male mice. Mice exposed to 1 and 10 days of WAS showed decreased unsupported rearing. A decreased total void area after 1 and 10 days of the WAS was observed, which was reversed in the 28-day-WAS group. There was an increased number of degranulated mast cells in the bladder of the 10-day-WAS group. The 1-day WAS exposure enhanced tonic contractile response to a muscarinic agonist, carbachol, which was reversed by 5-HT3 receptor antagonist pre-incubation. Interestingly, the 28-day WAS group showed a similar tonic contractile response to the control group. Our findings provide more insightful information about using 1-day WAS as an acute psychological stress model, and stress exposure longer than 10 days did not produce anxiety-like behavior and urinary bladder impairment.

CD4+ T-cell subsets are associated with chronic stress effects in newly diagnosed anxiety disorders

AimPrior research has indicated a connection between CD4+ T cells and the development of anxiety, but the specific CD4+ T cell subsets linked to anxiety disorders remain uncertain. Our study seeks to investigate the relationship between distinct CD4+ T cell subsets and anxiety, as well as to explore whether CD4+ T cell subsets mediate the effect of chronic psychological stress on anxiety. Methods56 eligible matched participants were recruited in Peking Union Medical College Hospital. The diagnosis was made based on DSM-5 diagnostic criteria. The severity of anxiety and depression symptoms was assessed using the Hamilton Anxiety Rating Scale and Hamilton Depression Rating Scale, respectively. The Life Events Scale (LES) evaluated the chronic stress level. CD4+ T cell subsets were characterized using multiparametric flow cytometry. To assess the impact of CD4+ T cells on the effect of chronic psychological stress on anxiety, Partial Least Squares Structural Equation Modeling (PLS-SEM) analysis was employed. ResultsWe discovered fifteen notably distinct CD4+ T-cell subsets in anxiety disorder patients compared to healthy controls. Multiple linear regression analysis unveiled an association between anxiety severity and CD27+CD45RA− Th cells, CD27+CD28+ Tregs, and the total Life Events Scale (LES) score. The PLS-SEM analysis demonstrated that CD4+ T cell subsets and LES could explain 80.2% of the variance in anxiety. Furthermore, it was observed that CD27+CD28+ Th/Treg cells acted as inverse mediators of the effects of LES on anxiety (P = 0.031). ConclusionsDrug naïve anxiety disorder patients exhibited significant alterations in numerous CD4+ T-cell subsets. Specifically, the memory subset of CD27+CD45RA− Th cells and the naïve subset of CD27+CD28+ Treg cells were found to be independent factors associated with the severity of anxiety. Additionally, the CD27+CD28+ Th and Treg cell subsets played a significant mediating role in the influence of long-term psychological stress on anxiety.

An antihypertensive drug-AT1 inhibitor attenuated BRCA development promoted by chronic psychological stress via Ang II/PARP1/FN1 pathway

Chronic psychological stress contributes to the occurrence of cancer and activates the renin-angiotensin system (RAS). However, the mechanisms by which RAS promotes the progression of breast cancer (BRCA) under chronic psychological stress are remain unknown. In this study, we observed elevated levels of Angiotensin II (Ang II) in both serum and BRCA tissue under chronic stress, leading to accelerated BRCA growth in a mouse model. An antihypertensive drug, candesartan (an AT1 inhibitor), effectively attenuated Ang II-induced cell proliferation and metastasis. Utilizing mass spectrometry and weighted gene co-expression network analysis (WGCNA), we identified fibronectin 1 (FN1) as the hub protein involved in chronic stress-Ang II/AT1 axis. Focal adhesion pathway was identified as a downstream signaling pathway activated during the progression of chronic stress. Depletion of FN1 significantly attenuated Ang II-induced proliferation and metastasis of BRCA cells. Poly (ADP-ribose) polymerase 1 (PARP1) was found to bind to the DNA promoter of FN1, leading to the transcription of FN1. Ang II upregulated PARP1 expression, resulting in increased FN1 levels. Recombinant FN1 partially restored the progress of BRCA malignancy induced by the Ang II/PARP1 pathway. In vivo, candesartan reversed the progressive effect of chronic psychological stress on BRCA. In clinical samples, Ang II levels in both serum and tumor tissues are higher in stressed patients compared to control patients. Serum Ang II levels were positively correlated with chronic stress indicators. In conclusion, our study demonstrated that chronic psychological stress accelerates the malignancy of BRCA, and the AT1 inhibitor candesartan counteracts these effects by suppressing the Ang II-AT1 axis and the downstream PARP1/FN1/focal adhesion pathway.

Abstract B001: The effect of chronic psychological stress during puberty and early adulthood on breast cancer risk and development

Abstract Breast cancer is the second most common cancer among women in the United States. Puberty is a well-established sensitive period in women when breast cancer (BC) risk is increased by the physical environment for example exposure to chemical carcinogens, synthetic estrogens, endocrine disrupters, radiation, etc. However, relatively little is known about effects of exposure to chronic psychological stress from the social environment during this time period (puberty and early adulthood). In previous studies using the Sprague-Dawley rat model of spontaneous mammary cancer, chronically heightened glucocorticoid stress reactivity arising from imposed social isolation after weaning increased duration of glucocorticoid release in response to everyday stressors, impeded mammary gland ductal development, and caused earlier and more aggressive mammary gland cancer incidence during adulthood. However due to the period of isolation lasting from weaning to death, a critical time period in which these changes occurred was not established. Here we found that chronic social isolation only during puberty and early adulthood results in alterations in mammary gland gene expression patterns and preservation of mammary stem/progenitor cells. We have observed that social isolation beginning at five weeks and ending at 21 weeks leads to a 4-fold increase in the key metabolic lipogenic enzymes ATP citrate lyase (ACLY; p-value = 0.008), 2-fold increase in acetyl-CoA carboxylase (Acaca; p-value=0.01), and 1.88-fold change in stearoyl-CoA desaturase 1 (Scd1; p-value = 0.50). Interestingly, we have also observed that social isolation during this time period, leads to a slight decrease (0.70-fold change) in hexokinase 2 (HK2; p-value= 0.007). Regarding mammary stem/progenitor cell preservation, we found that social isolation beginning at five weeks and ending at 17 weeks leads to a significant increase in the number of mammary gland stem/progenitor cells (isolated by FACS sorting). This correlation was only observed in response to corticosterone reactivity, and null to exposure to estrogen or progesterone. In summary, our findings suggest that social isolation during puberty and early adulthood correlates to increased glucocorticoid exposure resulting in metabolic reprogramming in the mammary gland and inappropriate preservation of mammary stem/progenitor cells. Altogether these factors may increase the risk of mammary cancer occurrence later in adulthood. Citation Format: Briana Banks, Matthew Brady. The effect of chronic psychological stress during puberty and early adulthood on breast cancer risk and development [abstract]. In: Proceedings of the 16th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2023 Sep 29-Oct 2;Orlando, FL. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2023;32(12 Suppl):Abstract nr B001.

1843MO The effect of chronic psychological stress on the efficacy of first-line therapy of ICIs in advanced NSCLC (STRESS-LUNG-1 trial)

1843MO The effect of chronic psychological stress on the efficacy of first-line therapy of ICIs in advanced NSCLC (STRESS-LUNG-1 trial)

Chronic psychological stress promotes breast cancer pre-metastatic niche formation by mobilizing splenic MDSCs via TAM/CXCL1 signaling

BackgroundEmerging studies have identified chronic psychological stress as an independent risk factor influencing breast cancer growth and metastasis. However, the effects of chronic psychological stress on pre-metastatic niche (PMN) formation and the underlying immunological mechanisms remain largely unknown.MethodsThe effects and molecular mechanisms of chronic unpredictable mild stress (CUMS) on modulating tumor-associated macrophages (TAMs) and PMN formation were clarified by multiplex immunofluorescence technique, cytokine array, chromatin immunoprecipitation, the dual-luciferase reporter assay, and breast cancer xenografts. Transwell and CD8+ T cytotoxicity detection were used to analyze the mobilization and function of myeloid-derived suppressor cells (MDSCs). mCherry-labeled tracing strategy and bone marrow transplantation were applied to explore the crucial role of splenic CXCR2+/+ MDSCs facilitating PMN formation under CUMS.ResultsCUMS significantly promoted breast cancer growth and metastasis, accompanied by TAMs accumulation in the microenvironment. CXCL1 was identified as a crucial chemokine in TAMs facilitating PMN formation in a glucocorticoid receptor (GR)-dependent manner. Interestingly, the spleen index was significantly reduced under CUMS, and splenic MDSCs were validated as a key factor mediating CXCL1-induced PMN formation. The molecular mechanism study revealed that TAM-derived CXCL1 enhanced the proliferation, migration, and anti-CD8+ T cell functions of MDSCs via CXCR2. Moreover, CXCR2 knockout and CXCR2−/−MDSCs transplantation significantly impaired CUMS-mediated MDSC elevation, PMN formation, and breast cancer metastasis.ConclusionOur findings shed new light on the association between chronic psychological stress and splenic MDSC mobilization, and suggest that stress-related glucocorticoid elevation can enhance TAM/CXCL1 signaling and subsequently recruit splenic MDSCs to promote PMN formation via CXCR2.Graphical

Brain-gut-liver axis: Chronic psychological stress promotes liver injury and fibrosis via gut in rats.

The effect of chronic psychological stress on hepatitis and liver fibrosis is concerned. However, its mechanism remains unclear. We investigated the effect and mechanism of chronic psychological stress in promoting liver injury and fibrosis through gut. Sixty male SD rats were randomly assigned to 6 groups. Rat models of chronic psychological stress (4 weeks) and liver fibrosis (8 weeks) were established. The diversity of gut microbiota in intestinal feces, permeability of intestinal mucosa, pathologies of intestinal and liver tissues, collagen fibers, protein expressions of toll-like receptor 4 (TLR4), myeloid differentiation factor 88 (MyD88), nuclear factor kappa β (NF-κβ), tumor necrosis factor α (TNF-α) and interleukin 1 (IL-1) in liver tissue, liver function and coagulation function in blood and lipopolysaccharide (LPS) in portal vein blood were detected and analyzed. The diversities and abundances of gut microbiota were significant differences in rats among each group. The pathological lesions of intestinal and liver tissues, decreased expression of occludin protein in intestinal mucosa, deposition of collagen fibers and increased protein expression of TLR4, MyD88, NF-κβ, TNF-α and IL-1 in liver tissue, increased LPS level in portal vein blood, and abnormalities of liver function and coagulation function, were observed in rats exposed to chronic psychological stress or liver fibrosis. There were significant differences with normal rats. When the dual intervention factors of chronic psychological stress and liver fibrosis were superimposed, the above indicators were further aggravated. Chronic psychological stress promotes liver injury and fibrosis, depending on changes in the diversity of gut microbiota and increased intestinal permeability caused by psychological stress, LPS that enters liver and acts on TLR4, and active LPS-TLR4 pathway depend on MyD88. It demonstrates the possibility of existence of brain-gut-liver axis.

Abstract 24: The effect of chronic psychological stress during puberty and early adulthood on mammary gland development and mammary cancer risk in adulthood

Abstract Breast cancer is the second most common cancer among women in the United States. Puberty is a well-established sensitive period in women when breast cancer (BC) risk is increased by the physical environment for example exposure to chemical carcinogens, synthetic estrogens, endocrine disrupters, radiation, etc. However, relatively little is known about effects of exposure to chronic psychological stress from the social environment during this time period (puberty and early adulthood). In previous studies using the Sprague-Dawley rat model of spontaneous mammary cancer, chronically heightened glucocorticoid stress reactivity arising from imposed social isolation after weaning increased duration of glucocorticoid release in response to everyday stressors, impeded mammary gland ductal development, and caused earlier and more aggressive mammary gland cancer incidence during adulthood. However due to the period of isolation lasting from weaning to death, a critical time period in which these changes occurred was not established. Here we found that chronic social isolation only during puberty and early adulthood results in alterations in mammary gland gene expression patterns and preservation of mammary stem/progenitor cells. We have observed that social isolation beginning at five weeks and ending at 21 weeks leads to a 4-fold increase in the key metabolic lipogenic enzymes ATP citrate lyase (ACLY; p-value = 0.008), 2-fold increase in acetyl-CoA carboxylase (Acaca; p-value=0.01), and 1.88-fold change in stearoyl-CoA desaturase 1 (Scd1; p-value = 0.50). Interestingly, we have also observed that social isolation during this time period, leads to a slight decrease (0.70-fold change) in hexokinase 2 (HK2; p-value= 0.007). Regarding mammary stem/progenitor cell preservation, we found that social isolation beginning at five weeks and ending at 17 weeks leads to a significant increase in the number of mammary gland stem/progenitor cells (isolated by FACS sorting). This correlation was only observed in response to corticosterone reactivity, and null to exposure to estrogen or progesterone. In summary, our findings suggest that social isolation during puberty and early adulthood correlates to increased glucocorticoid exposure resulting in metabolic reprogramming in the mammary gland and inappropriate preservation of mammary stem/progenitor cells. Altogether these factors may increase the risk of mammary cancer occurrence later in adulthood. Citation Format: Briana Banks, Marianna Johnson, Joscelyn Hoffmann, Hannah You, Matt Piron, Suzanne Conzen, Martha McClintock, Matthew Brady. The effect of chronic psychological stress during puberty and early adulthood on mammary gland development and mammary cancer risk in adulthood [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 24.

The anxiogenic effects of adolescent psychological stress in male and female mice

Adolescence is a period of transition during which there is extensive development of the brain and the hypothalamic-pituitary-adrenal axis. However, the term adolescence is broad and covers a number of important developmental periods ranging from pre-pubescence to sexual maturity. Using a predator stress model, we investigated the effects of chronic psychological stress on anxiety-like, depression-like, and social behaviours in male and female mice during early adolescence, when mice are pre-pubertal, and late adolescence, when mice are sexually mature. All stressed mice showed hyperactivity and increased anxiety-like behaviours. The anxiogenic effects were generally more pronounced in mice exposed to late, rather than early adolescent stress, but were clearly evident when stress was experienced at either timepoint. Risk assessment behaviours were also affected by the stress treatments, but the direction of these changes were sometimes sex- and age-specific. Surprisingly, mice stressed during adolescence showed no depressive-like behaviours as adults. This study provides evidence that adolescent psychological stress has pronounced long-term anxiogenic effects but that the precise behavioural phenotype differs based on sex and the sub-stage of adolescence during which the individual is exposed.

The Effect of Chronic Psychological Stress on Lower Urinary Tract Function: An Animal Model Perspective.

Chronic psychological stress can affect urinary function and exacerbate lower urinary tract (LUT) dysfunction (LUTD), particularly in patients with overactive bladder (OAB) or interstitial cystitis–bladder pain syndrome (IC/BPS). An increasing amount of evidence has highlighted the close relationship between chronic stress and LUTD, while the exact mechanisms underlying it remain unknown. The application of stress-related animal models has provided powerful tools to explore the effect of chronic stress on LUT function. We systematically reviewed recent findings and identified stress-related animal models. Among them, the most widely used was water avoidance stress (WAS), followed by social stress, early life stress (ELS), repeated variable stress (RVS), chronic variable stress (CVS), intermittent restraint stress (IRS), and others. Different types of chronic stress condition the induction of relatively distinguished changes at multiple levels of the micturition pathway. The voiding phenotypes, underlying mechanisms, and possible treatments of stress-induced LUTD were discussed together. The advantages and disadvantages of each stress-related animal model were also summarized to determine the better choice. Through the present review, we hope to expand the current knowledge of the pathophysiological basis of stress-induced LUTD and inspire robust therapies with better outcomes.

Sini San Inhibits Chronic Psychological Stress-Induced Breast Cancer Stemness by Suppressing Cortisol-Mediated GRP78 Activation.

Chronic psychological stress is closely correlated with breast cancer growth and metastasis. Sini San (SNS) formula is a classical prescription for relieving depression-related symptoms in traditional Chinese medicine (TCM). Current researches have suggested that chronic psychological stress is closely correlated with cancer stem cells (CSCs) and endoplasmic reticulum (ER) stress. This study aimed to investigate the effects of chronic psychological stress on ER stress-mediated breast cancer stemness and the therapeutic implication of SNS. Chronic psychological stress promoted lung metastasis in 4T1 breast tumor-bearing mice and increased the stem cell-like populations and stemness-related gene expression. Meanwhile, GRP78, a marker of ER stress, was significantly increased in the breast tumors and lung metastases under chronic psychological stress. As a biochemical hallmark of chronic psychological stress, cortisol dramatically enhanced the stem cell-like populations and mammospheres formation by activating GRP78 transcriptionally. However, GRP78 inhibitors or shRNA attenuated the stemness enhancement mediated by cortisol. Similarly, SNS inhibited chronic psychological stress-induced lung metastasis and stemness of breast cancer cells, as well as reversed cortisol-induced stem cell-like populations and mammospheres formation by attenuating GRP78 expression. Co-localization and co-immunoprecipitation experiments showed that SNS interrupted the interaction between GRP78 and LRP5 on the cell surface, thus inhibiting the Wnt/β-catenin signaling of breast CSCs. Altogether, this study not only uncovers the biological influence and molecular mechanism of chronic psychological stress on breast CSCs but also highlights SNS as a promising strategy for relieving GRP78-induced breast cancer stemness via inhibiting GRP78 activation.

Preclinical models of deep craniofacial nociception and temporomandibular disorder pain.

Chronic pain in temporomandibular disorder (TMD) is a common health problem. Cumulating evidence indicates that the etiology of TMD pain is complex with multifactorial experience that could hamper the developments of treatments. Preclinical research is a resource to understand the mechanism for TMD pain, whereas limitations are present as a disease-specific model. It is difficult to incorporate multiple risk factors associated with the etiology that could increase pain responses into a single animal. This article introduces several rodent models which are often employed in the preclinical studies and discusses their validities for TMD pain after the elucidations of the neural mechanisms based on the clinical reports. First, rodent models were classified into two groups with or without inflammation in the deep craniofacial tissues. Next, the characteristics of each model and the procedures to identify deep craniofacial pain were discussed. Emphasis was directed on the findings of the effects of chronic psychological stress, a major risk factor for chronic pain, on the deep craniofacial nociception. Preclinical models have provided clinically relevant information, which could contribute to better understand the basis for TMD pain, while efforts are still required to bridge the gap between animal and human studies.

Oxidative stress in the skin: Impact and related protection.

Skin, our first interface to the external environment, is subjected to oxidative stress caused by a variety of factors such as solar ultraviolet, infrared and visible light, environmental pollution, including ozone and particulate matters, and psychological stress. Excessive reactive species, including reactive oxygen species and reactive nitrogen species, exacerbate skin pigmentation and aging, which further lead to skin tone unevenness, pigmentary disorder, skin roughness and wrinkles. Besides these, skin microbiota are also a very important factor ensuring the proper functions of skin. While environmental factors such as UV and pollutants impact skin microbiota compositions, skin dysbiosis results in various skin conditions. In this review, we summarize the generation of oxidative stress from exogenous and endogenous sources. We further introduce current knowledge on the possible roles of oxidative stress in skin pigmentation and aging, specifically with emphasis on oxidative stress and skin pigmentation. Meanwhile, we summarize the science and rationale of using three well-known antioxidants, namely vitamin C, resveratrol and ferulic acid, in the treatment of hyperpigmentation. Finally, we discuss the strategy for preventing oxidative stress-induced skin pigmentation and aging.

Chronic Unpredictable Mild Stress Accelerates the Growth of Bladder Cancer in a Xenograft Mouse Model.

ObjectiveChronic psychological stress is common in patients with bladder cancer. An increasing number of evidence demonstrated that psychiatric disorder leads to worse prognostic outcomes in bladder cancer. This study was to investigate the effects of chronic psychological stress on the growth of bladder cancer and its potential mechanisms.MethodsA xenograft mouse model was established by subcutaneously implanting the human bladder cancer cell line T24 into nude mice. All of the tumor-bearing mice (N=20) were randomly separated into two groups. Mice in the control group were subjected to normal feeding conditions, while in another group, a chronic unpredictable mild stress (CUMS) model was established, in which mice were exposed to various types of stressors. Various analyses were performed on parameters including the tumor volume, tumor weight, expression of Caspase-3 and VEGF, proportion of Ki-67 positive cells (Ki-67 index), microvessel density (MVD) and serum concentrations of epinephrine and cortisol.ResultsIn the CUMS group, the growth of transplanted tumors was distinctly accelerated, with the weight of removed tumors at the end of experiment increased by 34.07% compared to that of the control. Serum levels of epinephrine and cortisol determined by ELISA were significantly increased by CUMS. Immunohistochemistry and Western blot analysis showed that the expression of Caspase-3 was downregulated, whereas the expression of VEGF was upregulated in the CUMS group. Meanwhile, CUMS could increase the Ki-67 index and MVD.ConclusionOur research supports the hypothesis that CUMS could affect the growth of bladder cancer in nude mice, indicating that the intervention of chronic psychological stress may be a possible therapeutic strategy for bladder cancer.

Psychological stress creates an immune-suppressive environment that increases the susceptibility of aged mice to Mycobacterium tuberculosis infection

Abstract Age is a risk factor for chronic infections, including tuberculosis (TB). A second compounding factor of TB susceptibility is psychological stress, which is particularly acute in older individuals. While the influence of psychological stress in TB is well documented, the mechanisms by which stress influences M.tb susceptibility in the elderly are almost completely unknown. To study the effects of chronic psychological stress on M.tb infection in old mice, we employed a mouse social stressor model (called social disruption stress or SDR) which involves repeated social defeat in subordinate mice. Young (3 month) and old (18 month) C57BL/6 mice were subjected to SDR and bronchial fluid (BF) and alveolar macrophages (AMs) were isolated by lung lavage. Our studies showed that SDR created an immune-suppressive lung environment in old mice, based on lower levels of pro-inflammatory cytokines and chemokines in bronchial fluid (BF) or their mRNA expression by AMs. AMs from old SDR mice compared to non-stressed mice were also deficient in their ability to mount an inflammatory cytokine response or induce MHC class II mRNA expression. To determine the effect of SDR on M.tb growth, young and old mice were subjected to SDR and infected with M.tb. At 30 days, SDR in both young and old mice reduced M.tb burden. However, this was transient as at 60 days M.tb burden was higher in old mice compared to young mice and SDR further significantly increased M.tb burden in old mice. Also we found that SDR at 60 days in old mice induced significantly higher levels of IL-10 and IL-17 mRNA in the lung, which favors growth of M.tb. In conclusion, our studies suggest that psychological stress during the initial stage of Mtb infection has long-term impact on the control of the infection.

Is Being Stressed Really that Bad? Mechanistic Pathways and Interventions for the Stress‐health Relationship

There is now considerable evidence from epidemiological and experimental studies demonstrating the profound impact that extensive periods of psychological stress have on physical and mental health. The impact is so profound that analyses using the Midlife in the United States (MIDUS) nationally representative longitudinal study have demonstrated that those in the highest quartile of a cumulative index of stress exposure across their lifetime compared to those in the lowest quartile have a 20% increased risk of dying over the next 12 years. More immediately, chronic stress exposure decreases engagement in core health behaviors like exercise and sleep, increases negative mood and conflicts with others, limits one’s ability to pay attention, and increases the risk of developing the common cold. All of these in turn negatively impact productivity and performance in school and work. The biological mechanisms linking psychological stress to these negative mental and physical health effects are now well documented and include the immune system, cellular aging, neuroendocrine system, and autonomic nervous system. In recent years, there has been important headway made on understanding how to combat the negative effects of stress – both through psychological interventions that increase psychological resilience to stress, and through targeting biological processes that are negatively impacted by stress. In particular, contemplative practices such as meditation and yoga have been shown to reduce stress and boost stress‐related biomarkers of disease, likely through the activation of the parasympathetic nervous system. When the body feels safe, such as in relaxed states of focused attention and when one feels a sense of belonging in a group setting (both of which are often the case in contemplative practice), their parasympathetic system is activated, allowing the body to enter a state of relaxation. Activation of the parasympathetic nervous system also puts the breaks on the sympathetic nervous system which is responsible for putting the body in the ‘fight or flight’ highly activated response. It is in this space of relaxed, parasympathetic activation, that the body can heal itself from the damage done by chronic stress, thus pointing to a key aspect to target with stress‐reduction interventions. This talk will focus on the biological underpinnings of the stress‐health relationship and the cutting edge science showing what we can do to reduce the negative effects of chronic psychological stress.

慢性心理应激对骨质疏松的影响

慢性心理应激对骨质疏松的影响

Chronic psychological stress impairs germinal center response by repressing miR-155

Germinal centers (GC) are vital to adaptive immunity. BCL6 and miR-155 are implicated in control of GC reaction and lymphomagenesis. FBXO11 causes BCL6 degradation through ubiquitination in B-cell lymphomas. Chronic psychological stress is known to drive immunosuppression. Corticosterone (CORT) is an adrenal hormone expressed in response to stress and can similarly impair immune functions. However, whether GC formation is disrupted by chronic psychological stress and its molecular mechanism remain to be elucidated. To address this issue, we established a GC formation model in vivo, and a GC B cell differentiation model in vitro. Comparing Naive B cells to GC B cells in vivo and in vitro, the differences of BCL6 and FBXO11 mRNA do not match the changes at the protein level and miR-155 levels that were observed. Next we demonstrated that CORT increase, induced by chronic psychological stress, reduced GC response, IgG1 antibody production and miR-155 level in vivo. The effect of chronic psychological stress can be blocked by a glucocorticoid receptor (GR) antagonist. Similarly, impaired GC B cell generation and isotope class switching were observed. Furthermore, we found that miR-155 and BCL6 expression were downregulated, but FBXO11 expression was upregulated in GC B cells treated with CORT in vitro. In addition, we demonstrated that miR-155 directly down-regulated FBXO11 expression by binding to its 3́-untranslated region. The subsequent overexpression of miR-155 significantly blocked the stress-induced impairment of GC response, due to changes in FBXO11 and BCL6 expression, as well as increased apoptosis in B cells both in vivo and in vitro. Our findings suggest perturbation of GC reaction may play a role in chronic psychological stress-induced immunosuppression through a glucocorticoid pathway, and miR-155-mediated post-transcriptional regulation of FBXO11 and BCL6 expression may contribute to the impaired GC response.

Decoding microglia responses to psychosocial stress reveals blood-brain barrier breakdown that may drive stress susceptibility

An animal’s ability to cope with or succumb to deleterious effects of chronic psychological stress may be rooted in the brain’s immune responses manifested in microglial activity. Mice subjected to chronic social defeat (CSD) were categorized as susceptible (CSD-S) or resilient (CSD-R) based on behavioral phenotyping, and their microglia were isolated and analyzed by microarray. Microglia transcriptomes from CSD-S mice were enriched for pathways associated with inflammation, phagocytosis, oxidative stress, and extracellular matrix remodeling. Histochemical experiments confirmed the array predictions: CSD-S microglia showed elevated phagocytosis and oxidative stress, and the brains of CSD-S but not CSD-R or non-stressed control mice showed vascular leakage of intravenously injected fluorescent tracers. The results suggest that the inflammatory profile of CSD-S microglia may be precipitated by extracellular matrix degradation, oxidative stress, microbleeds, and entry and phagocytosis of blood-borne substances into brain parenchyma. We hypothesize that these CNS-centric responses contribute to the stress-susceptible behavioral phenotype.

Does the diurnal cycle of cortisol explain the relationship between physical performance and cognitive function in older adults?

BackgroundRegular physical activity is a promising strategy to treat and prevent cognitive decline. The mechanisms that mediate these benefits are not fully clear but physical activity is thought to attenuate the harmful effects of chronic psychological stress and hypercortisolism on cognition. However, the circadian pattern of cortisol secretion is complex and it is not known which aspects are most closely associated with increased cognitive function and better physical performance. This is the first study to simultaneously measure cognitive function, the diurnal cycle of salivary cortisol and physical performance in older adults, without cognitive impairment (n = 30) and with amnestic Mild Cognitive Impairment (aMCI) (n = 30).ResultsRegression analysis showed that better cognitive function was associated with better physical performance. A greater variance in cortisol levels across the day from morning to evening was associated with better cognitive function and physical performance.ConclusionsThe results support the idea that a more dynamic cortisol secretion pattern is associated with better cognitive function and physical performance even in the presence of cognitive impairment, but our results could not confirm a mediating role in this relationship.