Acute stress induces long-lasting alterations in the dopaminergic system of female mice

AbstractStress is a risk factor for many neuropsychiatric disorders, and the mesolimbic dopamine (DA) pathway is a crucial node of vulnerability. Despite the high prevalence of stress-related neuropsychiatric disorders in women, preclinical knowledge on the impact of stress on neural circuitry has predominantly been acquired in males. Here, we examine how a non-social stressor impacts the effect of DA neurotransmission on social and reward-related behaviors in female mice. Acute stress exposure attenuated the anti-social effects of photoinhibiting ventral tegmental area (VTA) DA neurons and transformed photoactivation of these cells into an anti-social signal. Fast-scan cyclic voltammetry (FSCV) revealed an enhancement in optogenetically-induced DA release after stress. 60 days after stress, mice showed distinct patterns of intra-cranial self-stimulation of VTA DA neurons. Our results reveal the impact stress exerts on females and show that neural and behavioral changes induced by acute stress exposure are still present months later.

Download Full-text

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

Proceedings of The Nutrition Society ◽

10.1017/s0029665120004413 ◽

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.

Download Full-text

Residual avoidance: a new consistent and repeatable readout of chronic stress-induced conflict anxiety reversible by antidepressant treatment

10.1101/414029 ◽

2018 ◽

Author(s):

Thomas D. Prevot ◽

Keith A. Misquitta ◽

Corey Fee ◽

Dwight F. Newton ◽

Dipashree Chatterjee ◽

...

Keyword(s):

Chronic Stress ◽

Stressful Life Events ◽

Acute Stress ◽

Antidepressant Treatment ◽

Behavioral Changes ◽

Mild Stress ◽

Stress Exposure ◽

Experimenter Bias ◽

Critical Insight ◽

Consistent Response

AbstractStress-related illnesses such as major depressive and anxiety disorders are characterized by maladaptive responses to stressful life events. Chronic stress-based animal models have provided critical insight into the understanding of these responses. Currently available assays measuring chronic stress-induced behavioral states in mice are limited in their design (short, not repeatable, sensitive to experimenter-bias) and often inconsistent. Using the Noldus PhenoTyper apparatus, we identified a new readout that repeatedly assesses behavioral changes induced by chronic stress in two mouse models i.e. chronic restraint stress (CRS) and chronic unpredictable mild stress (UCMS). The PhenoTyper test consists of overnight monitoring of animals’ behavior in home-cage setting before, during and after a 1hr light challenge applied over a designated food zone. We tested the reproducibility and reliability of the PhenoTyper test in assessing the effects of chronic stress exposure, and compared outcomes with commonly-used tests. While chronic stress induced heterogeneous profiles in classical tests, CRS- and UCMS-exposed mice showed a very consistent response in the PhenoTyper test. Indeed, CRS and UCMS mice continue avoiding the lit zone in favor of the shelter zone. This “residual avoidance” after the light challenge, lasted for hours beyond termination of the challenge, was not observed after acute stress and was consistently found throughout stress exposure in both models. Chronic stress-induced residual avoidance was alleviated by chronic imipramine treatment but not acute diazepam administration. This behavioral index should be instrumental for studies aiming to better understand the trajectory of chronic stress-induced deficits and potentially screen novel anxiolytics and antidepressants.

Download Full-text

Loss of CREBRF Reduces Anxiety-like Behaviors and Circulating Glucocorticoids in Male and Female Mice

Endocrinology ◽

10.1210/endocr/bqaa163 ◽

2020 ◽

Vol 161 (11) ◽

Author(s):

Krystle A Frahm ◽

Akeem A Williams ◽

Ashlee N Wood ◽

Michael C Ewing ◽

Polly E Mattila ◽

...

Keyword(s):

Stress Responses ◽

Acute Stress ◽

Plasma Corticosterone ◽

Affective States ◽

Male And Female ◽

Female Mice ◽

Glucocorticoid Signaling ◽

Plus Maze ◽

The Impact

Abstract Glucocorticoid signaling controls many key biological functions ranging from stress responses to affective states. The putative transcriptional coregulator CREB3 regulatory factor (CREBRF) reduces glucocorticoid receptor levels in vitro, suggesting that CREBRF may impact behavioral and physiological outputs. In the present study, we examined adult male and female mice with global loss of CREBRF (CrebrfKO) for anxiety-like behaviors and circulating glucocorticoids in response to various acute stress conditions. Results demonstrate that both male and female CrebrfKO mice have preserved locomotor activity but reduced anxiety-like behaviors during the light–dark box and elevated plus maze. These behavioral phenotypes were associated with lower plasma corticosterone after restraint stress. Further studies using unhandled female mice also demonstrated a loss of the diurnal circulating corticosterone rhythm in CrebrfKO mice. These results suggest that CREBRF impacts anxiety-like behavior and circulating glucocorticoids in response to acute stressors and serves as a basis for future mechanistic studies to define the impact of CREBRF in glucocorticoid-associated behavioral and physiological responses.

Download Full-text

Immunization with Mycobacterium vaccae NCTC 11659 prevents the development of PTSD-like sleep and behavioral phenotypes after sleep disruption and acute stress in mice

10.1101/2020.05.07.082859 ◽

2020 ◽

Author(s):

Samuel J. Bowers ◽

Sophie Lambert ◽

Shannon He ◽

Christopher A. Lowry ◽

Monika Fleshner ◽

...

Keyword(s):

Acute Stress ◽

Behavioral Changes ◽

Sleep Disruption ◽

Stress Resilience ◽

Behavioral Phenotypes ◽

Mycobacterium Vaccae ◽

Beta Power ◽

The Impact ◽

Inadequate Sleep ◽

Improve Health

AbstractBecause regular sleep disruption can increase vulnerability to stress-related psychiatric disorders, there is a need to explore novel countermeasures to increase stress resilience after inadequate sleep. In this study, we explored the impact of 5 days of intermittent sleep disruption on vulnerability to acute social defeat stress in mice, and investigated the ability of the environmental, immunomodulatory bacterium Mycobacterium vaccae NCTC 11659 (MV) to promote stress resilience in that context. We found that mice receiving sleep disruption plus acute stress developed sleep and behavioral phenotypes that had some features of human posttraumatic stress disorder (PTSD) including reduced NREM delta power and increased NREM beta power in post-stress sleep EEG, persistent increases in sleep fragmentation and the REM:Sleep ratio, and behavioral changes. Importantly, immunization with heat-killed MV prevented the development of this phenotype. These results support further research into novel, microbial-based countermeasures to improve health and increase resilience to sleep disruption.

Download Full-text

Dynamic behavioral and molecular changes induced by chronic stress exposure in mice

10.1101/2021.05.07.443011 ◽

2021 ◽

Author(s):

Thomas Damien Prevot ◽

Dipashree Chatterjee ◽

Jaime Knoch ◽

Sierra Codeluppi ◽

Keith A Misquitta ◽

...

Keyword(s):

Chronic Stress ◽

Inhibitory Synapses ◽

Stress Exposure ◽

Male And Female ◽

Molecular Changes ◽

Female Mice ◽

Network Analyses ◽

Underlying Mechanisms ◽

The Impact ◽

Integrative Network

Depression is a leading cause of disabilities around the world, and the underlying mechanisms involved in its pathophysiology are broad and complex. Exposure to chronic stress is a risk factor for developing depressive-symptoms and contributes to cellular and molecular changes precipitating the emergence of symptoms. In the brain, excitatory neurons, inhibitory interneurons and supporting astroglial cells are all sensitive to chronic stress exposure and are known to be impaired in depression. Using an animal model of chronic stress, we assessed the impact of variable durations of chronic stress on the emergence of behavioral deficits and associated molecular changes in the prefrontal cortex (PFC), brain region highly sensitive to stress and impaired in depression. Mice were exposed to up to 35 days of chronic restraint stress and were assessed weekly on behavioral tests measuring anxiety and anhedonia. PFC Protein and RNA levels of specific markers of excitatory, inhibitory synapses and astroglia were quantified using western blot and qPCR, respectively. Correlation and integrative network analyses were used to investigated the impact of chronic stress on the different compartments. Results showed that chronic stress induces anxiety-like behaviors within 7 days, while anhedonia-like behaviors were observed only after 35 days. At the molecular level, alterations of many markers were observed, in particular with longer exposure to chronic stress. Finally, correlation analyses and integrative network analyses revealed that male and female mice react differently to chronic stress exposure and that some markers seem to be more correlated to behaviors deficits in males than in females. Our study demonstrate that chronic induces a dynamic changes that can be observed at the behavioral and molecular levels, and that male and female mice, while exhibiting similar symptoms, have different underlying pathologies.

Download Full-text

The Impact of Chronic Stress and Eating Concern on Acylated Ghrelin Following Acute Psychological Stress in Healthy Men

Stresses ◽

10.3390/stresses1010003 ◽

2021 ◽

Vol 1 (1) ◽

pp. 16-29

Author(s):

Christine Fahrngruber-Velasquez ◽

Kalina Duszka ◽

Jürgen König

Keyword(s):

Food Intake ◽

Chronic Stress ◽

Eating Behavior ◽

Stress Responses ◽

Acute Stress ◽

Stressful Situation ◽

Acylated Ghrelin ◽

Stress Exposure ◽

Control Situation ◽

The Impact

Stress, mood, and eating behavior play an important role in appetite and weight regulation. In particular, ghrelin, as the only known orexigenic hormone, has been suggested to be an influential mediator in food intake responses to stress. The exact role of ghrelin in the hypothalamic–pituitary–adrenal axis is still unknown and further challenged by the psychological aspects of stress and eating behavior. This study aimed to assess the effect of chronic stress and subjective concern about eating on acute stress-induced changes in acylated ghrelin. In a 2-day study, sixteen healthy male participants were confronted with a stressful situation as well as a control situation. Additional measurements of heart rate, subjective hunger ratings, and subjective mood ratings were made to assess successful acute stress induction. The linear mixed model approach revealed a significant effect of acute stress on acylated ghrelin for a study-day*chronic-stress interaction (p < 0.001). Concern about eating did not affect acylated ghrelin levels after acute stress exposure. The significant interaction showed that lower chronic stress exposure was associated with a stronger acylated ghrelin response after acute stress exposure versus control condition. At the same time, participants with higher chronic stress exposure showed a blunted acylated ghrelin response after acute stress exposure compared to the control situation. Our findings indicate that chronic stress exposure can influence acylated ghrelin response after acute stress encounters, possibly affecting subsequent food intake and explaining the often diverse outcome in measurements of acute stress responses.

Download Full-text

The impact of acute stress on the neural processing of food cues in bulimia nervosa: Replication in two samples.

Journal of Abnormal Psychology ◽

10.1037/abn0000242 ◽

2017 ◽

Vol 126 (5) ◽

pp. 540-551 ◽

Cited By ~ 10

Author(s):

Brittany Collins ◽

Lauren Breithaupt ◽

Jennifer E. McDowell ◽

L. Stephen Miller ◽

James Thompson ◽

...

Keyword(s):

Bulimia Nervosa ◽

Acute Stress ◽

Neural Processing ◽

Food Cues ◽

Two Samples ◽

The Impact

Download Full-text

Comparing the Impact of Religious Discourse on HIV/AIDS in Islam and Christianity in Africa

Vanderbilt Undergraduate Research Journal ◽

10.15695/vurj.v8i0.3490 ◽

2012 ◽

Vol 8 ◽

Cited By ~ 4

Author(s):

Sloane Speakman

Keyword(s):

Social Factors ◽

Negative Relationship ◽

Hiv Prevalence ◽

Religious Discourse ◽

Prevalence Rates ◽

The Social ◽

High Prevalence ◽

Islam And Christianity ◽

Sub Saharan ◽

The Impact

In examining the strikingly high prevalence rates of HIV in many parts of Africa, reaching as high as 5% in some areas, how does the discourse promoted by the predominant religions across the continent, Islam and Christianity, affect the outlook of their followers on the epidemic? This question becomes even more intriguing after discovering the dramatic difference in rate of HIV prevalence between Muslims and Christians in Africa, confirmed by studies that have found a negative relationship to exist between HIV prevalence and being Muslim in Africa, even in Sub-Saharan African nations. Why does this gap in prevalence rates exist? Does Islam advocate participating in less risky behavior more so than Christianity? By comparing the social construction, epidemiological understanding and public responses among Muslim populations in Africa with Christian ones, it becomes apparent that many similarities exist between the two regarding discourse and that, rather than religious discourse itself, other social factors, such as circumcision practices, contribute more to the disparity in HIV prevalence than originally thought.

Download Full-text

Characterizing the Role of HMG-CoA Reductase in Aryl Hydrocarbon Receptor-Mediated Liver Injury in C57BL/6 Mice

Scientific Reports ◽

10.1038/s41598-019-52001-2 ◽

2019 ◽

Vol 9 (1) ◽

Cited By ~ 2

Author(s):

Peter Dornbos ◽

Amanda Jurgelewicz ◽

Kelly A. Fader ◽

Kurt Williams ◽

Timothy R. Zacharewski ◽

...

Keyword(s):

Liver Injury ◽

Aryl Hydrocarbon Receptor ◽

Cholesterol Biosynthesis ◽

Competitive Inhibitor ◽

Cholesterol Homeostasis ◽

Hepatic Glycogen ◽

Alcoholic Fatty Liver ◽

Female Mice ◽

Aryl Hydrocarbon ◽

The Impact

Abstract The aryl hydrocarbon receptor (AHR) is a ligand-activated transcription factor. The prototypical ligand of the AHR is an environmental contaminant called 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). TCDD exposure is associated with many adverse health outcomes in humans including non-alcoholic fatty liver disease (NAFLD). Previous studies suggest that AHR ligands alter cholesterol homeostasis in mice through repression of genes involved in cholesterol biosynthesis, such as Hmgcr, which encodes the rate-limiting enzyme of cholesterol biosynthesis called 3-hydroxy-3-methyl-glutaryl coenzyme A reductase (HMGCR). In this study, we sought to characterize the impact of HMGCR repression in TCDD-induced liver injury. C57BL/6 mice were exposed to TCDD in the presence or absence of simvastatin, a competitive inhibitor of HMGCR. Simvastatin exposure decreased TCDD-induced hepatic lipid accumulation in both sexes, but was most prominent in females. Simvastatin and TCDD (S + T) co-treatment increased hepatic AHR-battery gene expression and liver injury in male, but not female, mice. In addition, the S + T co-treatment led to an increase in hepatic glycogen content that coincides with heavier liver in female mice. Results from this study suggest that statins, which are amongst the most prescribed pharmaceuticals, may protect from AHR-mediated steatosis, but alter glycogen metabolism and increase the risk of TCDD-elicited liver damage in a sex-specific manner.

Download Full-text

Premature ovarian ageing following heterozygous loss of Senataxin

MHR Basic science of reproductive medicine ◽

10.1093/molehr/gaaa080 ◽

2020 ◽

Author(s):

G N Subramanian ◽

M Lavin ◽

H A Homer

Keyword(s):

Dna Damage ◽

Neurodegenerative Disorder ◽

Dna Helicase ◽

Dna Integrity ◽

Ovarian Activity ◽

Homozygous Mutation ◽

Female Mice ◽

Mating Trial ◽

High Prevalence

Abstract Premature loss of ovarian activity before 40 years of age is known as primary ovarian insufficiency (POI) and occurs in ∼1% of women. A more subtle decline in ovarian activity, known as premature ovarian ageing (POA), occurs in ∼10% of women. Despite the high prevalence of POA, very little is known regarding its genetic causation. Senataxin (SETX) is an RNA/DNA helicase involved in repair of oxidative stress-induced DNA damage. Homozygous mutation of SETX leads to the neurodegenerative disorder, ataxia oculomotor apraxia type 2 (AOA2). There have been reports of POI in AOA2 females suggesting a link between SETX and ovarian ageing. Here, we studied female mice lacking either one (Setx+/−) or both (Setx−/−) copies of SETX over a 12- to 14-month period. We find that DNA damage is increased in oocytes from 8-month-old Setx+/− and Setx−/− females compared with Setx+/+ oocytes leading to a marked reduction in all classes of ovarian follicles at least 4 months earlier than typically occurs in female mice. Furthermore, during a 12-month long mating trial, Setx+/− and Setx−/− females produced significantly fewer pups than Setx+/+ females from 7 months of age onwards. These data show that SETX is critical for preventing POA in mice, likely by preserving DNA integrity in oocytes. Intriguingly, heterozygous Setx loss causes an equally severe impact on ovarian ageing as homozygous Setx loss. Because heterozygous SETX disruption is less likely to produce systemic effects, SETX compromise could underpin some cases of insidious POA.

Download Full-text