scholarly journals A Polymorphism in the Crhr1 Gene Determines Stress Vulnerability in Male Mice

Endocrinology ◽  
2014 ◽  
Vol 155 (7) ◽  
pp. 2500-2510 ◽  
Author(s):  
Christiana Labermaier ◽  
Christine Kohl ◽  
Jakob Hartmann ◽  
Christian Devigny ◽  
Andre Altmann ◽  
...  
Keyword(s):  
Chronic Stress ◽  
Social Stress ◽  
Genetic Variations ◽  
Risk Haplotype ◽  
Nucleotide Polymorphisms ◽  
Stress Exposure ◽  
Long Term Effects ◽  
Cd1 Mice ◽  
Early Trauma

Chronic stress is a risk factor for psychiatric disorders but does not necessarily lead to uniform long-term effects on mental health, suggesting modulating factors such as genetic predispositions. Here we address the question whether natural genetic variations in the mouse CRH receptor 1 (Crhr1) locus modulate the effects of adolescent chronic social stress (ACSS) on long-term stress hormone dysregulation in outbred CD1 mice, which allows a better understanding of the currently reported genes × environment interactions of early trauma and CRHR1 in humans. We identified 2 main haplotype variants in the mouse Crhr1 locus that modulate the long-term effects of ACSS on basal hypothalamic-pituitary-adrenal axis activity. This effect is likely mediated by higher levels of CRHR1, because Crhr1 mRNA expression and CRHR1 binding were enhanced in risk haplotype carriers. Furthermore, a CRHR1 receptor antagonist normalized these long-term effects. Deep sequencing of the Crhr1 locus in CD1 mice revealed a large number of linked single-nucleotide polymorphisms with some located in important regulatory regions, similar to the location of human CRHR1 variants implicated in modulating gene × stress exposure interactions. Our data support that the described gene × stress exposure interaction in this animal model is based on naturally occurring genetic variations in the Crhr1 gene associated with enhanced CRHR1-mediated signaling. Our results suggest that patients with a specific genetic predisposition in the CRHR1 gene together with an exposure to chronic stress may benefit from a treatment selectively antagonizing CRHR1 hyperactivity.

scholarly journals The impact of chronic stress and eating types on active ghrelin levels in response to acute stress

2020 ◽  
Vol 79 (OCE2) ◽  
Author(s):  
Christine Fahrngruber ◽  
Kalina Duszka ◽  
Jürgen König
Keyword(s):  
Chronic Stress ◽  
Eating Behavior ◽  
Social Stress ◽  
Acute Stress ◽  
Stress Test ◽  
Primary Objective ◽  
Trier Social Stress Test ◽  
Relaxation Techniques ◽  
Stress Exposure ◽  
The Impact

AbstractChronic stress is associated with impacting eating behavior, namely food choice and energy intake, with a shift towards more palatable and energy dense foods. Additionally, eating behavior is influenced by other psychological factors like mood and emotions. The categorization of people into eating types such as restrained, emotional, and external eaters has gained attraction. Reported changes in eating behavior due to psychological stress are only occasionally accompanied by measures of physiological hunger through ghrelin. The primary objective of this study was to investigate how chronic stress and acute cortisol reactivity affect active ghrelin secretion and how these outcomes account for different eating types. 16 healthy, young males (age: 23 ± 3 years, BMI: 22.5 ± 1.3kg/m2) with low (n = 8) and average-to-high (n = 8) chronic stress level were subjected to the Trier Social Stress Test (TSST) and a control version on two separate days. Active ghrelin, cortisol, glucose, and heart rate were measured throughout the test. Subjects rated their hunger by means of visual analog scale and current mood was assessed with the Positive and Negative Affect Scale (PANAS). In addition, participants filled out the Dutch Eating Behavior Questionnaire (DEBQ) to account for their subjective eating behavior. Overall ghrelin values where higher on the test day compared to the control day. Ghrelin values were also higher during the time leading up to the stress or control test (TSST) than during the conclusion of said tests. On both days, mean values for active ghrelin where higher in individuals with low chronic stress exposure compare to those with average-to-high chronic stress exposure. While values from test to control day decreased for lower stressed participants, they slightly increased for higher stressed participants. Cortisol responders displayed higher ghrelin values on test day than cortisol non-responders, but this association inverted for the control day. Results indicate that chronic stress influences acute stress response and further alters active ghrelin production, which in turn can influence eating behavior. Replication in a greater group of participants of differing weight and sex could yield a greater understanding of stress induced eating. Factors such as relaxation techniques and coping mechanisms could further improve our knowledge and evaluate treatment possibilities.

scholarly journals Influence of long term stress exposure on somatisation symptoms outcome

2004 ◽  
Vol 4 (4) ◽  
pp. 28-31
Author(s):  
Sabaheta Hasić ◽  
Emina Kiseljaković ◽  
Radivoj Jadrić ◽  
Belma Zečević ◽  
Nešina Avdagić ◽  
...  
Keyword(s):  
Chronic Stress ◽  
Control Group ◽  
Stress Exposure ◽  
War Stress ◽  
Control Subjects ◽  
Study Results ◽  
Significant Difference ◽  
Student’S T ◽  
And Control

Long term stress exposure results in somatisation symptoms appearance. Cardiovascular, respiratory, gastrointestinal and muscle-bone symptoms arise because of intensified activity of autonomic nervous system caused by chronic stress. The aim of the study was to examine the relationship between long term war stress exposure and appearance of somatisation. 40 students of health-care faculties in Sarajevo, of both sexes, were included in investigation and divided in two groups-somatisation and control. Somatisation group subjects (N=20) lived in B&H under war conditions, from 1992-1995. Control subjects (N=20) spent the same period outside B&H. For evaluation of somatisation symptoms we used SCL-90-R test. The obtained data were statistically evaluated using Student’s t-test and χ2 test. Confidence level was set at ρ < 0,05. Our results showed statistically significant difference in somatisation level between somatisation and control subjects group. Different intensity of appearance of certain symptoms in male and female was established. The score of somatisation dimension between somatisation and control group showed statistically significant level (p < 0,0001). Study results confirmed correlation of chronic stress exposure (living in war environment) and somatisation symptom appearance. Individual organic systems had various level of symptom expression. The influence of sex on intensity of individual symptoms of somatisation is possible.

scholarly journals Ovarian status dictates the neuroinflammatory and behavioral consequences of sub-chronic stress exposure in middle-aged female mice

2019 ◽  
Author(s):  
Rand S. Eid ◽  
Stephanie E. Lieblich ◽  
Sarah J. Wong ◽  
Liisa A.M. Galea
Keyword(s):  
Frontal Cortex ◽  
Chronic Stress ◽  
Ovarian Hormones ◽  
Stress Exposure ◽  
Middle Aged ◽  
Aged Mice ◽  
Ovariectomized Mice ◽  
Ovarian Status ◽  
Immunomodulatory Properties

AbstractOvarian hormones influence the outcomes of stress exposure and are implicated in stress-related disorders including depression, yet their roles are often complex and seemingly contradictory. Importantly, depression and stress exposure are associated with immune dysregulation, and ovarian hormones have immunomodulatory properties. However, how ovarian hormones can influence the inflammatory outcomes of stress exposure is poorly understood. Here, we examined the effects of long-term ovariectomy on the behavioral and neuroinflammatory outcomes of sub-chronic stress exposure in middle-aged mice. Briefly, sham-operated and ovariectomized mice were assigned to non-stress groups or exposed to 6 days of variable stress. Mice were assessed on a battery of behavioral tests, and cytokine concentrations were quantified in the frontal cortex and hippocampus. In the frontal cortex, postsynaptic density protein-95 expression was examined as an index of excitatory synapse number and/or stability, and phosphorylated mitogen-activated protein kinases (MAPKs) were measured to explore potential cell signaling pathways elicited by stress exposure and/or ovarian hormones. Long-term ovariectomy modified the central cytokine profile by robustly reducing cytokine concentrations in the frontal cortex and modestly increasing concentrations in the hippocampus. Under non-stress conditions, long-term ovariectomy also reduced extracellular signal-regulated kinase (ERK) phosphoprotein expression in the frontal cortex and increased some measures of depressive-like behavior. The effects of sub-chronic stress exposure were however more pronounced in sham-operated mice. Notably, in sham-operated mice only, sub-chronic stress exposure increased IL-1β and IL-6:IL-10 ratio in the frontal cortex and hippocampus and reduced pERK1/2 expression in the frontal cortex. Further, although sub-chronic stress exposure increased anhedonia-like behavior regardless of ovarian status, it increased passive-coping behavior in sham-operated mice only. These data indicate that long-term ovariectomy has potent effects on the central cytokine milieu and dictates the neuroinflammatory and behavioral effects of sub-chronic stress exposure in middle-aged mice. These findings therefore suggest that the immunomodulatory properties of ovarian hormones are of relevance in the context of stress and possibly depression.

scholarly journals Sex differences in chronic social stress models in mice

2019 ◽  
Author(s):  
Orit Furman ◽  
Michael Tsoory ◽  
Alon Chen
Keyword(s):  
Sex Differences ◽  
Animal Models ◽  
Mouse Model ◽  
Treatment Response ◽  
Chronic Stress ◽  
Social Stress ◽  
Molecular Mechanisms ◽  
Body Weight Loss ◽  
Chronic Social Stress

AbstractChronic stress creates an allostatic overload that may lead to mood disorders such as anxiety and depression. Modern causes of chronic stress in humans are mostly social in nature, relating to work and relationship stress. Research into neural and molecular mechanisms of vulnerability and resilience following chronic social stress (CSS) is ongoing and uses animal models to discover efficient prevention strategies and treatments. To date, most CSS studies have neglected the female sex and used male-focused aggression-based animal models such as chronic social defeat stress (CSDS). Accumulating evidence on sex differences suggests differences in the stress response, the prevalence of stress-related illness and the treatment response, indicating that researchers should expand CSS investigation to include female-focused protocols alongside the popular CSDS protocols. Here, we describe a novel female mouse model of CSS and a parallel modified male mouse model of CSDS in C57BL/6 mice. These new models enable the investigation of vulnerability, coping and downstream effectors mediating long-term consequences of CSS in both sexes. Our data demonstrate sex differences during CSS and for many weeks following CSS. Female mice are more prone to body weight loss during CSS and hyperactive anxious behavior following CSS. Both sexes show disturbances in social interaction, but only stressed male mice show long-term changes in neuroendocrine function and memory performance after fear conditioning. We discuss future avenues of research using these models to investigate mechanisms pertaining to sensitivity to CSS as well as treatment response profiles, in a sex-suitable manner.

Adolescent vulnerability to cardiovascular consequences of chronic social stress: Immediate and long-term effects of social isolation during adolescence

2015 ◽  
Vol 76 (1) ◽  
pp. 34-46 ◽  
Author(s):  
Fábio C. Cruz ◽  
Josiane O. Duarte ◽  
Rodrigo M. Leão ◽  
Luiz F.V. Hummel ◽  
Cleopatra S. Planeta ◽  
...  
Keyword(s):  
Social Isolation ◽  
Social Stress ◽  
Long Term Effects ◽  
Chronic Social Stress

scholarly journals Effects of maternal exposure to social stress during pregnancy: consequences for mother and offspring

Reproduction ◽  
2013 ◽  
Vol 146 (5) ◽  
pp. R175-R189 ◽  
Author(s):  
Paula J Brunton
Keyword(s):  
Hpa Axis ◽  
Prenatal Stress ◽  
Social Stress ◽  
Maternal Stress ◽  
Reproductive Potential ◽  
Maternal Behaviour ◽  
Stress Exposure ◽  
Prenatally Stressed ◽  
In Pregnancy

A suboptimalin uteroenvironment, for example, as a result of maternal stress, can have detrimental effects on the pregnancy and long-term adverse ‘programming’ effects on the offspring. This article focuses on the effects of prenatal social stress on the mother, her pregnancy and the offspring, since these issues have ethological relevance in both animals and humans. The consequences of social stress exposure depend on when during pregnancy the stress occurs, and many of the effects on the offspring are sex specific. Social stress during early pregnancy tends to result in pregnancy loss, whereas stress exposure later in pregnancy, when the mother has already invested considerable resources in the foetuses, results in programmed offspring of low birth weight: a risk factor for various adulthood diseases. Neuroendocrine and behavioural responses to stress in the offspring are particularly sensitive to foetal programming by prenatal stress, indicated by enhanced hypothalamo-pituitary–adrenal (HPA) axis responses and increased anxiety behaviour, which result from permanent changes in the offspring's brain. The dysregulation of HPA axis function may also interfere with other systems, for example, the hypothalamic–pituitary–gonadal axis, as there is evidence for alterations in steroidogenesis, reproductive potential and impaired reproductive/social behaviours in prenatally stressed offspring. Prenatal social stress also programmes future maternal behaviour, highlighting the potential for negative phenotypes to be transmitted to future generations. The possible mechanisms through which maternal stress during pregnancy is transmitted to the foetuses and the foetal brain is programmed by prenatal stress and the potential to overwrite programming of the offspring are discussed.

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