A mechanism converting psychosocial stress into mononuclear cell activation

Bierhaus, Angelika; Wolf, Jutta M.; Andrassy, Martin; Rohleder, Nicolas; Humpert, Per M.; Petrov, Dimitri; Ferstl, Roman; Eynatten, Maximilian von; Wendt, Thoralf; Rudofsky, Gottfried; Joswig, Martina; Morcos, Michael; Schwaninger, Markus; McEwen, Bruce S.; Kirschbaum, Clemens; Nawroth, Peter P.

doi:10.1073/pnas.0438019100

Cited by 814 publications

(602 citation statements)

References 61 publications

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“…A CSD study in BALB/c CSD mice and C57BL/6 aggressor mice also reported increased plasma levels of TNF and proinflammatory interleukins; although the standard CSD protocol was used there were no correlations between cytokine level and number of bite wounds received (Savignac et al, 2011a). In healthy humans, acute psychosocial stress causes increased blood levels of pro-inflammatory cytokines (Bierhaus et al, 2003) and blood levels of TNF and IL-6 are increased in depression (Dowlati et al, 2010). In addition, the spleens of CSD mice were hypertrophic, consistent with invasion and expansion of activated immune cells.…”

Section: Discussionmentioning

confidence: 99%

Mouse social stress induces increased fear conditioning, helplessness and fatigue to physical challenge together with markers of altered immune and dopamine function

et al. 2014

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In neuropsychiatry, animal studies demonstrating causal effects of environmental manipulations relevant to human aetiology on behaviours relevant to human psychopathologies are valuable. Such valid models can improve understanding of aetio-pathophysiology and preclinical discovery and development of new treatments. In depression, specific uncontrollable stressful life events are major aetiological factors, and subsequent generalized increases in fearfulness, helplessness and fatigue are core symptoms or features. Here we exposed adult male C57BL/6 mice to 15-day psychosocial stress with loss of social control but minimal physical wounding. One cohort was assessed in a 3-day test paradigm of motor activity, fear conditioning and 2-way avoid-escape behaviour on days 16-18, and a second cohort was assessed in a treadmill fatigue paradigm on days 19 and 29, followed by the 3-day paradigm on days 30-32. All tests used a physical aversive stimulus, namely mild, brief electroshocks. Socially stressed mice displayed decreased motor activity, increased fear acquisition, decreased 2-way avoid-escape responding (increased helplessness) and increased fatigue. They also displayed increased plasma TNF and spleen hypertrophy, and adrenal hypertrophy without hyper-corticoidism. In a third cohort, psychosocial stress effects on brain gene expression were assessed using next generation sequencing. Gene expression was altered in pathways of inflammation and G-protein coupled receptors in prefrontal cortex and amygdala; in the latter, expression of genes important in dopamine function were de-regulated including down-regulated Drd2, Adora2a and Darpp-32. This model can be applied to identify targets for treating psychopathologies such as helplessness or fatigue, and to screen compounds/biologics developed to act at these targets. AbstractIn neuropsychiatric research, animal studies that demonstrate causal effects of environmental manipulations relevant to human aetiological factors on emotional and cognitive behaviours relevant to human psychopathologies are valuable. Such valid animal models can be useful for improved understanding of aetio-pathophysiology and preclinical discovery and development of new treatments. In depression, specific uncontrollable stressful life events are major aetiological factors, and subsequent generalized increases in fearfulness, helplessness and fatigue are core psychopathology symptoms or features. In the present study we exposed adult male C57BL/6 mice to an environmental manipulation of 15-day psychosocial stress with loss of social control but with minimal physical wounding. One cohort of stressed and control mice was assessed in a novel 3-day test paradigm of motor activity, fear conditioning and 2-way avoid-escape behaviour on days 16-18, and a second cohort was assessed in a treadmill fatigue paradigm on days 19 and 29, followed by the 3-day paradigm on days 30-32. All tests used a physical aversive stimulus, namely mild, brief electroshocks. The socially stressed mice displayed dec...

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Section: Discussionmentioning

confidence: 99%

Mouse social stress induces increased fear conditioning, helplessness and fatigue to physical challenge together with markers of altered immune and dopamine function

et al. 2014

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“…Mechanisms mediating the adverse effect of stress on CVD risk include exaggerated or dysregulated immune activation in response to psychosocial stress [1,3]. Acute mental stress elicited using behavioral or cognitive tasks is known to up-regulate pro-inflammatory gene expression in peripheral mononuclear blood cells resulting in the synthesis and release of inflammatory cytokines [4,5]. Evidence shows that the binding activity of the nuclear factor-kappaB (NF-kB), a key mediator of inducible transcription in the immune system and inflammatory genes, is enhanced by exposure to acute stress in humans.…”

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confidence: 99%

“…Evidence shows that the binding activity of the nuclear factor-kappaB (NF-kB), a key mediator of inducible transcription in the immune system and inflammatory genes, is enhanced by exposure to acute stress in humans. This is likely mediated through adrenergic receptor stimulation [4,6,7] and appears to be inversely related to glucocorticoid responses [7,8].…”

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confidence: 99%

Post-menopausal Women Exhibit Greater Interleukin-6 Responses to Mental Stress Than Older Men

2016

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Background Acute stress triggers innate immune responses and elevation in circulating cytokines including interleukin-6 (IL-6). The effect of sex on IL-6 responses remains unclear due to important limitations of previous studies. Purpose The purpose of this study was to examine sex differences in IL-6 responses to mental stress in a healthy, older (postmenopausal) sample accounting for several moderating factors. Methods Five hundred six participants (62.9 ± 5.60 years, 55 % male) underwent 10 min of mental stress consisting of mirror tracing and Stroop task. Blood was sampled at baseline, after stress, and 45 and 75 min post-stress, and assayed using a high sensitivity kit. IL-6 reactivity was computed as the mean difference between baseline and 45 min and between baseline and 75 min post-stress. Main effects and interactions were examined using ANCOVA models. Results There was a main effect of time for the IL-6 response (F 3,1512 = 201.57, p = <.0001) and a sex by time interaction (F 3,1512 = 17.07, p = <.001). In multivariate adjusted analyses, IL-6 reactivity was significantly greater in females at 45 min (M = 0.37 ± 0.04 vs. 0.20 ± 0.03 pg/mL, p = .01) and at 75 min (M = 0.57 ± 0.05 vs. 0.31 ± 0.05 pg/mL, p = .004) post-stress compared to males. Results were independent of age, adiposity, socioeconomic position, depression, smoking and alcohol consumption, physical activity, statin use, testing time, task appraisals, hormone replacement, and baseline IL-6. Other significant predictors of IL-6 reactivity were lower household wealth, afternoon testing, and baseline IL-6. Conclusions Healthy, post-menopausal females exhibit substantially greater IL-6 responses to acute stress. Inflammatory responses if sustained over time may have clinical implications for the development and maintenance of inflammatoryrelated conditions prevalent in older women.

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“…Psychological stress promotes NF-κB activation, providing a channel for translating psychological stress into mononuclear cell activation 22 . In contrast, two key omega-3 PUFA, eicosapentaenoic acid (EPA) and docosahexanoic acid (DHA), can substantially decrease lipopolysaccharideinduced (LPS-induced) TNF-α expression by blocking NF-κB activation 21 .…”

Section: Diet and Inflammationmentioning

confidence: 99%

Omega-3 Fatty Acids and Stress-Induced Immune Dysregulation: Implications for Wound Healing

Kiecolt‐Glaser¹,

Glaser²,

Christian³

2016

Military Medicine

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Stress-related immune alterations can be consequential for health; they can enhance susceptibility to infectious agents and influence the severity of infectious disease, diminish the strength of immune responses to vaccines, reactivate latent viruses, and slow wound healing. Furthermore, stressful events and negative emotions promote systemic proinflammatory cytokine production while reducing beneficial local production of proinflammatory cytokines at the wound site that are important for wound healing. Dietary omega-3 and omega-6 polyunsaturated fatty acids (PUFA) also influence systemic inflammation; high proportions of omega-6 to omega-3 boost inflammation, while omega-3 has anti-inflammatory properties. Additionally, the limited evidence thus far suggests that omega-3 PUFA may enhance local inflammatory responses at wound sites. Moreover, an individual's dietary proportion of omega-3 to omega-6 may influence the magnitude of inflammatory responses to stressful events. Thus, wound healing and surgery provide exemplars of how stress and depression can interact with the diet to influence important clinical outcomes.

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A mechanism converting psychosocial stress into mononuclear cell activation

Cited by 814 publications

References 61 publications

Mouse social stress induces increased fear conditioning, helplessness and fatigue to physical challenge together with markers of altered immune and dopamine function

Mouse social stress induces increased fear conditioning, helplessness and fatigue to physical challenge together with markers of altered immune and dopamine function

Post-menopausal Women Exhibit Greater Interleukin-6 Responses to Mental Stress Than Older Men

Omega-3 Fatty Acids and Stress-Induced Immune Dysregulation: Implications for Wound Healing

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