Chronic Stress Research Articles

Promoting Resilience in Healthcare Workers: A Preventative Mental Health Education Program.

Healthcare workers face greater risks for mental health conditions and chronic stress due to the demanding nature of their roles. The COVID-19 pandemic exacerbated these challenges and increased vulnerabilities to long-term mental health conditions. The present study adapts an existing resilience-based educational workshop program to address the time constraints and unique needs of the healthcare workforce in a post-COVID-19 world. Expanded from its initial focus on resilience, the workshop curriculum incorporates psychoeducation on common mental health issues. Between July 2022 and June 2024, a 15 min "huddle" format offered on-site training to equip HCWs in a large urban health system with coping strategies to prevent, manage, and recover from stress. Attendance and anonymous feedback were collected at each session via brief electronic surveys. Participant responses (n = 1403) obtained immediately post-huddle suggested positive impact on stress management, perceived leadership support, and resilience. Findings show the potential of brief huddles to improve mental health and resilience in healthcare workers and similar workforces. Our findings support the efficacy of brief, evidence-based educational huddles in enhancing resilience, mental health awareness, and coping skills among HCWs. This model holds significant potential for widespread implementation across healthcare and other high-stress workplaces.

The Role of Immune Cells and Signaling Pathways in Diabetic Eye Disease: A Comprehensive Review.

Diabetic eye disease (DED) encompasses a range of ocular complications arising from diabetes mellitus, including diabetic retinopathy, diabetic macular edema, diabetic keratopathy, diabetic cataract, and glaucoma. These conditions are leading causes of visual impairments and blindness, especially among working-age adults. Despite advancements in our understanding of DED, its underlying pathophysiological mechanisms remain incompletely understood. Chronic hyperglycemia, oxidative stress, inflammation, and neurodegeneration play central roles in the development and progression of DED, with immune-mediated processes increasingly recognized as key contributors. This review provides a comprehensive examination of the complex interactions between immune cells, inflammatory mediators, and signaling pathways implicated in the pathogenesis of DED. By delving in current research, this review aims to identify potential therapeutic targets, suggesting directions of research for future studies to address the immunopathological aspects of DED.

Chronic stress in adulthood results in microvascular dysfunction and subsequent depressive-like behavior

Depression is a prevalent mental disorder characterized by unknown pathogenesis and challenging treatment. Recent meta-analyses reveal an association between cardiovascular risk factors and an elevated risk of depression. Despite this, the precise role of vascular injury in depression development remains unclear. In this investigation, we assess vascular system function in three established animal models of depression— chronic unpredictable mild stress (CUMS), chronic social defeat stress (CSDS) and maternal separation (MS)—utilizing ultrasonography and laser Doppler measurement. All three model animals exhibit anhedonia and despair-like behavior. However, significant microvascular dysfunction (not macrovascular) is observed in animals subjected to CUMS and CSDS models, while such dysfunction is absent in the MS model. Statistical analysis further indicates that microcirculation dysfunction is not only associated with depression-like behavior but is also intricately involved in the development of depression in the CUMS and CSDS models. Furthermore, our study has proved for the first time that endothelial nitric oxide synthase-deficient (eNOS+/−) mice, which is a classic model of vascular endothelial injury, showed depression-like behavior which occurred two months later than microvascular dysfunction. Notably, the mitigation of microvascular dysfunction successfully reverses depression-like behavior in eNOS+/− mice by enhancing nitric oxide production. In conclusion, this study unveils the pivotal role of microvascular dysfunction in the onset of depression induced by chronic stress in adulthood and proposes that modulating microvascular function may serve as a potential intervention in the treatment of depression.

Identification and experimental validation of hub genes underlying depressive-like behaviors induced by chronic social defeat stress.

Introduction: Major depressive disorder (MDD), characterized by severe neuropsychiatric symptoms and significant cognitive deficits, continues to present both etiological and therapeutic challenges. However, the specific underlying mechanisms and therapeutic targets remain unclear. Methods: We analyzed human postmortem dorsolateral prefrontal cortex (dlPFC) samples from MDD patients using datasets GSE53987 and GSE54568, identifying three key genes: AGA, FBXO38, and RGS5. To model depressive-like behavior, we employed chronic social defeat stress (CSDS) and subsequently measured the expression of AGA, FBXO38, and RGS5 in the dlPFC using qPCR and Western blot analysis following CSDS exposure. Results: CSDS significantly induced depressive-like behavior, and both the protein and transcriptional expression levels of AGA, FBXO38, and RGS5 in the dlPFC of mice were markedly reduced after stress, consistent with findings from datasets GSE53987 and GSE54568. Conclusion: Our research suggests that AGA, FBXO38, and RGS5 are potential biomarkers for MDD and could serve as valuable targets for MDD risk prediction.

Psychiatry and sensation: the epigenetic links.

A complex interaction among sensory, social and epigenetic determinants in psychiatric conditions was described across all age strata. The high prevalence of mental disorders in individuals with sensory deficits might be attributed to the interaction among social isolation, cognitive functioning and sensory processing. The epigenetic implications of such interactions were examined: environmental and social factors can affect gene expression and impact the pathogenesis of psychiatric disorders also through sensory processing. This article discussed the role of social determinants, in other words, social isolation, loneliness and chronic stress, in promoting psychiatric disorders and, in a vicious circle, sensory deficits (vision, hearing, olfaction and somatosensation). We emphasized the importance of integrating social, sensory and epigenetic factors to target different treatments for psychiatric conditions.

Effects of Chronic Stress and Comfort Food in Testicular Morphology in Adult Wistar Rats.

To investigate the effect of chronic stress on testicular morphology in adult Wistar rats, as well as the impact of comfort food consumption on these parameters. 32 Wistar rats (10 weeks old) were divided into four groups: control (C), stressed (S), control + comfort food (C+CF), and stressed + comfort food (S+CF). Chronic stress was induced by the restraint method during 8 weeks in groups S and S+CF, while groups C and C+CF were maintained under normal conditions. Groups C and S received a standard rat chow diet, while groups C+CF and S+CF received both the standard chow and comfort food (Froot Loops®). After 8 weeks of experiment, all animals were euthanized and the testes were collected for histomorphometric, immunohistochemical and gene expression analysis. Comfort food was preferred over standard chow in groups C+CF and S+CF, but this preference was more preeminent in stressed animals (S+CF). The consumption of comfort food resulted in testicular weight reduction. The seminipherous epithelium was reduced in group S in comparison to controls. While comfort food also reduced the epithelium in C+CF in comparison to controls, for group S+CF the comfort food ameliorated the stress-induced damage. The cell proliferation rate and the relative expression of StAR and BLC2 genes were similar between the groups. Both chronic stress and comfort food consumption resulted in morphological alterations of the testes but the consumption of comfort foods during chronic stress partially prevented the stress-induced detrimental effects on testes.

Use of Five Complementary Health Modalities Relevant to Lifestyle Medicine: A 2020 Survey of Northern California Adults Aged 35-79 years.

Complementary health (CH) modalities can be used as part of a Lifestyle Medicine (LM) approach to preventing and managing chronic conditions. This cross-sectional study used data for respondents to the 2020 (N = 6,715) and 2014/2015 (N = 11,112) cycles of a Northern California health plan member survey to estimate use in 2020 of five CH modalities relevant to LM: vegetarian/vegan diet, mind/body stress management techniques (MBSM), yoga/Pilates, massage therapy, and prayer/spiritual practice. Use was estimated by sex and racial/ethnic group (White, Black, Latino, Asian/PI)) for ages 35-64 and 65-79years and for adults 35-79years with diabetes, hypertension, heart disease, fair/poor sleep quality, and chronic stress. CH use in 2020 was compared to 2014/2015. In 2020, 53% of adults used ≥1 of these CH modalities, including 8.4% vegetarian/vegan diet, 25.8% MBSM, 23.7% prayer/spiritual practice, 16.5% yoga/Pilates, and 17.7% massage. Sex, age group, and racial/ethnic differences were seen in use of most CH modalities, and CH modality use varied by health condition. Significant increases from 2014/2015 to 2020 were seen in use of MBSM and yoga/Pilates, vegetarian/vegan diet, and prayer/spiritual practice. There is substantial opportunity to increase use of CH modalities within a LM approach to preventing and managing chronic health conditions.

Association between allostatic load and accelerated white matter brain aging: findings from the UK biobank.

White matter (WM) brain age, a neuroimaging-derived biomarker indicating WM microstructural changes, helps predict dementia and neurodegenerative disorder risks. The cumulative effect of chronic stress on WM brain aging remains unknown. In this study, we assessed cumulative stress using a multi-system composite allostatic load (AL) index based on inflammatory, anthropometric, respiratory, lipidemia, and glucose metabolism measures, and investigated its association with WM brain age gap (BAG), computed from diffusion tensor imaging data using a machine learning model, among 22 951 European ancestries aged 40 to 69 (51.40% women) from UK Biobank. Linear regression, Mendelian randomization, along with inverse probability weighting and doubly robust methods, were used to evaluate the impact of AL on WM BAG adjusting for age, sex, socioeconomic, and lifestyle behaviors. We found increasing one AL score unit significantly increased WM BAG by 0.29years in association analysis and by 0.33years in Mendelian analysis. The age- and sex-stratified analysis showed consistent results among participants 45-54 and 55-64years old, with no significant sex difference. This study demonstrated that higher chronic stress was significantly associated with accelerated brain aging, highlighting the importance of stress management in reducing dementia and neurodegenerative disease risks.

Breakdown of the blood-brain barrier in depressed mice induced by chronic unpredictable mild stress

BackgroundRecent studies have suggested potential impairment of the blood-brain barrier (BBB) in depression. However, due to the limited research and variability in animal models, further investigation using diverse and stable models is necessary. MethodsA male mouse model of depression was established using the chronic unpredictable mild stress (CUMS) protocol. Following model establishment, depression-like behaviors were assessed using the sucrose preference test, tail suspension test, and forced swimming test. Morphological changes in the hippocampus were examined through hematoxylin-eosin staining. BBB permeability was evaluated using the Evans blue leakage test, fluorescein sodium (NaF) leakage test, and serum S100B content assessment. Gene and protein expression levels of BBB-related proteins in the hippocampus were determined via real-time PCR, western blotting, and immunofluorescence assays. ResultsCUMS exposure induced depression-like behaviors, including reduced body weight gain, diminished sucrose preference, and prolonged immobility in both the tail suspension test and forced swimming test. While no significant pathological changes were observed in the hippocampus of either group, increased BBB permeability was noted in the CUMS group, as evidenced by enhanced NaF leakage into the brain parenchyma and elevated serum S100B levels. Gene expression analysis revealed downregulation of angiogenesis-related genes and tight junction proteins in the CUMS group. Additionally, protein levels of tight junction proteins Claudin-5 and ZO-1 were lower in the CUMS group compared to controls. LimitationsThis study is limited to a male mouse model, and the BBB in females is worth exploring in the future. ConclusionsIncreased BBB permeability and decreased expression of tight junction proteins Claudin5 and ZO-1 were observed in mice with CUMS-induced depression.

Commentary on Sergey Slonimsky’s essay “An Unwilling Scandalmonger: A Chronicle of Chronic Stress – 1943-1971” from the Book “Notes in the Margin of a Music Score”

Commentary on Sergey Slonimsky’s essay “An Unwilling Scandalmonger: A Chronicle of Chronic Stress – 1943-1971” from the Book “Notes in the Margin of a Music Score”

What makes medical students choose their residencies? Association between mental health of medical students and their choices of future medical specialties

Background: Excessive cognitive demands and chronic stress contribute to the occurrence of mental health problems among medical students. It may be hypothesized that the presence of such disturbances have an influence on their choices of post-graduate training programs. Objective: The aim of the study was to evaluate the state of mental health of medical students and to assess if there is any association between the prevalence of mental health problems and their residency choices. Materials and methods: 114 medical students were surveyed in terms of their residencies' choices and their mental health with the usage of validated psychological questionnaires. Results: 74 (64,91%) of medical students needed psychiatric or psychological treatment at some stage in their lives. Intensity of risky alcohol consumption was positively correlated with the choice of surgery (p=.0000) and negatively correlated with the choice of psychiatry (p=.0000). The severity of depressive symptoms was positively correlated with emergency medicine choice (p=.0479). Anxiety symptoms, eating disorders and autism spectrum severity symptoms were not significantly correlated with the choice of any medical specialty. Conclusions: Medical students were found seriously affected by mental health problems, what to some extent seemed to impact their future career choices.

Real-Time Imaging Assessment of Stress-Induced Vascular Inflammation Using Heartbeat-Synchronized Motion Compensation.

Chronic mental stress accelerates atherosclerosis through complicated neuroimmune pathways, needing for advanced imaging techniques to delineate underlying cellular mechanisms. While histopathology, ex vivo imaging, and snapshots of in vivo images offer promising evidence, they lack the ability to capture real-time visualization of blood cell dynamics within pulsatile arteries in longitudinal studies. An electrically tunable lens was implemented in intravital optical microscopy, synchronizing the focal plane with heartbeats to follow artery movements. ApoE-/- mice underwent 2 weeks of restraint stress before baseline imaging followed by 2 weeks of stress exposure in the longitudinal imaging, while nonstressed mice remained undisturbed. The progression of vascular inflammation was assessed in the carotid arteries through intravital imaging and histological analyses. A 4-fold reduction of motion artifact, assessed by interframe SD, and an effective temporal resolution of 25.2 Hz were achieved in beating murine carotid arteries. Longitudinal intravital imaging showed chronic stress led to a 6.09-fold (P=0.017) increase in myeloid cell infiltration compared with nonstressed mice. After 3 weeks, we observed that chronic stress intensified vascular inflammation, increasing adhered myeloid cells by 2.45-fold (P=0.031), while no significant changes were noted in nonstressed mice. Microcirculation imaging revealed increased circulating, rolling, and adhered cells in stressed mice's venules. Histological analysis of the carotid arteries confirmed the in vivo findings that stress augmented plaque area, myeloid cell and macrophage accumulation, and necrotic core volume while reducing fibrous cap thickness indicating accelerated plaque formation. We visualized the 3-dimensional structure of the carotid artery and 4-dimensional dynamics of the venules in the cremaster muscle. Dynamic focusing motion compensation intravital microscopy enabled subcellular resolution in vivo imaging of blood cell dynamics in beating arteries under chronic restraint stress in real time. This novel technique emphasizes the importance of advanced in vivo imaging for understanding cardiovascular disease.

Stress-mediated Activation of Ferroptosis, Pyroptosis, and Apoptosis Following Mild Traumatic Brain Injury Exacerbates Neurological Dysfunctions.

Nearly half of mild traumatic brain injury (mTBI) patients continue to experience residual neurological dysfunction, which may be attributed to exposure to stress. Ferroptosis, a newly discovered form of cell death, is increasingly recognized for its involvement in the pathophysiology of TBI. Understanding the mechanisms by which stress influences mTBI, particularly through ferroptosis, is crucial for the effective treatment and prevention of mTBI patients who are sensitive to stressful events. In our study, a mouse mTBI model was established. An acute restraint stress (RS) and a chronic unpredictable mild stress (CUMS) model then were applied to make acute and chronic stress, respectively. We found acute RS significantly delayed the recovery of reduced body weight and short-term motor dysfunctions and exacerbated cell insults and blood-brain barrier leakage caused by mTBI. Further studies revealed that acute RS exacerbates neuronal ferroptosis, pyroptosis, and apoptosis by promoting iron overloading in the neocortex following mTBI. Interestingly, the inhibition of ferroptosis with iron chelators, including deferoxamine and ciclopirox, reversed pyroptosis and apoptosis. Moreover, CUMS aggravated neurological dysfunctions (motor function, cognitive function, and anxiety-like behavior) and exacerbated brain lesion volume. CUMS also exacerbates ferroptosis, pyroptosis, and apoptosis by intensifying iron deposition, along with decreasing the expression of neuronal brain-derived neurotrophic factor and glucocorticoid receptor in the neocortex post mTBI. These effects were also mitigated by iron chelators. Our findings suggest that alleviating ferroptosis induced by iron deposition may represent a promising therapeutic approach for mTBI patients who have experienced stressful events.

Exploring the Cardiovascular Protective Effects of Baicalin: A Pathway to New Therapeutic Insights.

Cardiovascular disorders develop the highest rates of mortality and morbidity worldwide, emphasizing the need for novel pharmacotherapies. The Chinese medicinal plant S. baicalensis has a number of major active components, one of which is called baicalin. According to emerging research, baicalin reduces chronic inflammation, immunological imbalance, lipid metabolism, apoptosis, and oxidative stress. Baicalin improves endothelial function and protects the cardiovascular system from oxidative stress-induced cell injury by scavenging free radicals and inhibiting xanthine oxidase. Therefore, it helps prevent CVD such as hypertension, atherosclerosis, and cardiac arrest. In this review, the therapeutic effects of baicalein are discussed in relation to both the prevention and management of cardiovascular diseases.

Association of allostatic load with depression, anxiety, and suicide: a prospective cohort study

BackgroundAllostatic load (AL) is an objective measure of the biological components of chronic stress within clinical practice, potentially influencing depression, anxiety, and suicide. This study investigates the association between AL and these mental disorders. MethodsIn this cohort study of 333,017 adults, participants without prior diagnoses of depression, anxiety, or suicide were observed from March 13, 2006, to October 31, 2022. AL was estimated using 10 biomarkers reflecting metabolic, cardiovascular, and inflammatory dysregulation. Diagnoses were based on the International Classification of Diseases 10th Revision (ICD-10). We performed Cox proportional hazards models to assess the relationship between AL and these mental disorders. Additionally, we conducted subgroup analyses for sex, age, and Townsend Deprivation Index (TDI), along with sensitivity analyses. ResultsThe median follow-up period was 12.99 years. Over the follow-up period, 13,441 (4.04%) participants developed depression, 13,903 (4.17%) developed anxiety and 796 (0.24%) committed suicide. In fully adjusted model, individuals with high AL had an increased risk of depression (HR = 1.389, P = 8.38 ×10-27), anxiety (HR = 1.304, P = 5.82 ×10-19) and suicide (HR = 1.433, P = 4.46 ×10-3). Women and younger individuals with high AL were vulnerable to depression and anxiety, while moderate AL levels were significantly associated with suicide in men and younger participants. Moreover, individuals with middle and high AL had an elevated risk of comorbid depression and anxiety. ConclusionsHigh AL is positively associated with increased risks of depression, anxiety, and suicide, highlighting its potential as a predictive tool in mental health.

Chronic treatment with the antipsychotic lurasidone modulates the neuroinflammatory changes associated with the vulnerability to chronic mild stress exposure in female rats

Stress exposure is a key risk factor for the developmentof depressive-like conditions. However, despite the higher incidence of Major Depressive Disorder in the female population, classical stress-based experimental paradigms have primarily focused on males. In the present study, we used the well-established chronic mild stress (CMS) paradigm to investigate the development of anhedonia, a cardinal symptom of affective disorders, in the female animals and we also studied the potential effect of the antipsychotic drug lurasidone in normalizing the alterations brought about by stress exposure. We found that three weeks of CMS exposure produced a significant reduction of sucrose intake in 50% of the animals (vulnerable, CMS-V), whereas the others were resilient (CMS-R). The development of an anhedonic phenotype in CMS-V was associated with a significant elevation of different immune markers, such as Complement C3 and C4, and inflammatory cytokines, including INFß and Il1ß in dorsal and ventral hippocampus. Interestingly, sub-chronic treatment with the antipsychotic drug lurasidone was able to revert the anhedonic phenotype while normalizing most of the molecular alterations found in rats vulnerable to CMS exposure. This study extends the ability of lurasidone to normalize the anhedonic phenotype in CMS rats also to females. Moreover, we provide novel evidence on lurasidone’s potential effectiveness in treating mental disorders characterized by immune-inflammatory dysfunction.

Exercise alleviates CUS-induced depressive-like behaviors by modulating paracellular and transcellular permeability of the blood-brain barrier in the prefrontal cortex

BackgroundIncreased blood-brain barrier (BBB) permeability is implicated in the pathophysiology of major depressive disorder (MDD). While aerobic exercise has shown promise in mitigating MDD symptoms by potentially preserving BBB integrity, the detailed mechanisms remain unclear. This study explores these mechanisms to assess aerobic exercise's therapeutic potential for MDD. MethodsMale C57BL/6 J mice were used in this study to investigate the effects of aerobic exercise on CUS-induced BBB permeability and depressive-like behaviors. Chronic unpredictable stress (CUS)-induced MDD mouse models were divided into three groups: Control, CUS, and CUS+Exercise. We monitored body weight, blood S100β levels, and cytokines via ELISA. Claudin-5 and Caveolin-1 (CAV-1) expressions in the medial prefrontal cortex were evaluated using Western blotting and immunofluorescence. BBB permeability was assessed using biocytin-TMR and Alb-Alexa 594 tracers. Transmission electron microscopy was used to observe ultrastructural changes in the BBB directly. Depression-related behaviors were tested through several behavioral assays. ResultsCUS significantly increased CAV-1 expression and Alb-Alexa 594 leakage, suggesting enhanced transcellular BBB permeability. Despite unchanged Claudin-5 levels, its tight junction ultrastructure was altered, leading to increased biocytin-TMR leakage. Aerobic exercise ameliorated these disruptions, reduced inflammatory cytokines, and improved behavioral outcomes in CUS mice. ConclusionDisruptions in both paracellular and transcellular BBB pathways are pivotal in depression development. Aerobic exercise offers potential therapeutic benefits for MDD linked with BBB dysfunction by mitigating stress-induced structural and functional changes.

The comparative effects of probiotics on growth, antioxidant indices and intestinal histomorphology of broilers under heat stress condition.

Heat stress adversely affects both the productivity and well-being of chickens. Probiotics offer beneficial impacts on the health and growth performance of broilers. The current study investigates the influence of administering of Bacillus (including B. subtilis, B. licheniformis, B. coagulans, and B. indicus) and Lactobacillus (consisting of L. acidophilus, L. plantarum, L. buchneri, and L. rhamnosus) probiotics via drinking water, either singular or combined, on various aspects including growth performance, oxidative stress markers, carcass characteristics, fecal microbial composition, intestinal structure, and intestinal pH in broilers exposed to chronic heat stress. A total of 150 one-day-old broiler chicks were divided into 5 groups: (1) NC, negative control; (2) HS, birds exposed to chronic heat stress; (3) HSpBacil, exposed to chronic heat stress and received Bacillus probiotic; (4) HSpLAB, subjected to chronic heat stress and provided with Lactobacillus probiotic; (5) HSpMix, subjected to chronic heat stress and administered a combined probiotic from Bacillus and Lactobacillus. The HS group exhibited significantly reduced levels of growth performance, carcass traits, and notably affected oxidative stress indices, as well as intestinal pH and histomorphology in the birds. Additionally, the administered probiotics led to increased weight of lymphoid organs, enhanced body weight gain, and improved intestinal histomorphology. Furthermore, the probiotics decreased malondialdehyde and increased total antioxidant capacity in broilers. In conclusion, Bacillus and Lactobacillus probiotics, as single or multi-species, particularly Lactobacillus and combined probiotic, demonstrated potential in alleviating the adverse effects of heat stress in broiler chickens. They could serve as beneficial feed additives and growth enhancers.

Phosphatidic acid is involved in regulation of autophagy in neurons in vitro and in vivo.

Major depressive disorder (MDD) is a common and severe psychiatric disease, which does not only lead to variety of neuropsychiatric symptoms, but unfortunately in a relatively large proportion of cases also to suicide. The pathogenesis of MDD still requires definition. We have previously shown that ceramide is increased in the blood plasma of patients with MDD. In mouse models of MDD, which are induced by treatment with corticosterone or application of chronic unpredictable stress, increased blood plasma ceramide also increased and caused an inhibition of phospholipase D in endothelial cells of the hippocampus and reduced phosphatidic acid levels in the hippocampus. Here, we demonstrated that corticosterone treatment of PC12 cells resulted in reduced cellular autophagy, which is corrected by treatment with phosphatidic acid. In vivo, treatment of mice with corticosterone or chronic unpredictable stress also reduced autophagy in hippocampus neurons. Autophagy was normalized upon i.v. injection of phosphatidic acid in these mouse models of MDD. In an attempt to identify targets of phosphatidic acid in neurons, we demonstrated that corticosterone reduced levels of the ganglioside GM1 in PC-12 cells and the hippocampus of mice, which were normalized by treatment of cells or i.v. injection of mice with phosphatidic acid. GM1 application also normalized autophagy in cultured neurons. Phosphatidic acid and GM1 corrected stress-induced alterations in behavior, i.e., mainly anxiety and anhedonia, in experimental MDD in mice. Our data suggest that phosphatidic acid may regulate via GM1 autophagy in neurons.

18F]FDG Brain Imaging Assessment in Preclinical Acute and Chronic Stress Models Using Statistical Parametric Mapping

Previous studies have used [18F]FDG as a biomarker for depression, anxiety, or chronic stress in cancer patients1,2. However, they lack specific brain patterns and assessment in preclinical models, limiting their translational potential. Hence, we set out to establish preclinical [18F]FDG brain PET as a method to evaluate stress in vivo. Lean C57BL/6J mice were exposed to acute and chronic cooling, restraint, and surgical stress. Obese mice were on a high-fat diet for eight weeks and exposed to cooling and restraint stress. [18F]FDG was injected into fasted animals under brief isoflurane anesthesia via the tail vein. Following a 60-minute distribution phase during acute stress or one day after stress exposure (chronic), animals underwent static μPET/CT scans (Siemens® Inveon). Brain images were spatially normalized, and intensity normalization was performed using proportional and histogram-based scaling3 with PMOD (V. 3.8). Normalized images were analyzed using a brain atlas (M. Mirrione) to extract regional SUV and statistical parametric mapping (SPM12) for voxel-wise comparison. Overall, in lean mice, total brain [18F]FDG-uptake was significantly reduced across all stress models except for acute restraint, whereas total uptake was unaffected in obese mice. Subsequent brain atlas analysis of lean mice revealed changes in regional uptake for all stressors except for chronic cooling, while obese mice were affected by only acute and chronic restraint. Using SPM, we validated stress-specific hypo- and hypermetabolic areas in the brains of lean mice upon acute cooling, acute and chronic restraint, and surgery and in obese mice after chronic restraint (see Figure). We also identified overlapping areas in the brain stem and hypothalamus region following acute cooling and surgery, possibly due to post-surgical hypothermia. Our findings show that static [18F]FDG-imaging is a valuable tool for noninvasively assessing brain activity in a multitude of stress models and a suitable translational tool for stress research in mice. Please click on the 'PDF' for the full abstract!