HPA axis and aging in depression: systematic review and meta-analysis.: One of the most consistent findings in the biology of depression is an altered activity of the hypothalamic-pituitary-adrenal (HPA) axis. However, data concerning this issue have never been examined with a focus on the older population. Here we present a systematic review and meta-analysis, based on studies investigating levels of cortisol, adrenocorticotropic hormone (ACTH) and corticotropin-releasing hormone (CRH) in depressed participants older than 60 and compared with healthy controls. We f
HPA axis and cortisol
The hormonal stress response and its measurement.
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المكتبة البحثية897 works heldPeer-reviewed work held with its DOI and abstract, labelled with the study design its publication types report. None of it has been read or assessed, so nothing here may be cited as showing anything. Retracted work is held for the record but never listed; a review that a later version replaced is listed under its replacement and marked.
The HPA axis in bipolar disorder: Systematic review and meta-analysis.: Objectives: To provide a quantitative and qualitative synthesis of the available evidence on the role of Hypothalamic-Pituitary-Adrenal (HPA) axis in the pathophysiology of Bipolar Disorder (BD). Methods: Meta-analysis and meta-regression of case-control studies examining the levels of cortisol, ACTH, CRH levels. Systematic review of stress reactivity, genetic, molecular and neuroimaging studies related to HPA axis activity in BD. Results: Forty-one studies were included in the meta-analyses. BD
Depression and hypothalamic-pituitary-adrenal activation: a quantitative summary of four decades of research.: Objectives: To summarize quantitatively the literature comparing hypothalamic-pituitary-adrenal (HPA) axis function between depressed and nondepressed individuals and to describe the important sources of variability in this literature. These sources include methodological differences between studies, as well as demographic or clinical differences between depressed samples. Methods: The current study used meta-analytic techniques to compare 671 effect sizes (cortisol, adrenocorticotropic hormone,
The stress-buffering effect of acute exercise: Evidence for HPA axis negative feedback.: According to the cross-stressor adaptation hypothesis, physically trained individuals show lower physiological and psychological responses to stressors other than exercise, e.g. psychosocial stress. Reduced stress reactivity may constitute a mechanism of action for the beneficial effects of exercise in maintaining mental health. With regard to neural and psychoneuroendocrine stress responses, the acute stress-buffering effects of exercise have not been investigated yet. A sample of highly traine
Hypothalamic-pituitary-adrenal axis dysregulation and cortisol activity in obesity: A systematic review.: Background: Although there is substantial evidence of differential hypothalamic-pituitary-adrenal (HPA) axis activity in both generalized and abdominal obesity, consistent trends in obesity-related HPA axis perturbations have yet to be identified. Objectives: To systematically review the existing literature on HPA activity in obesity, identify possible explanations for inconsistencies in the literature, and suggest methodological improvements for future study. Data sources: Included papers used
Cortisol stress reactivity across psychiatric disorders: A systematic review and meta-analysis.: The hypothalamus-pituitary-adrenal (HPA) axis and its end product cortisol are essential for an adequate response to stress. Considering the role of stress as a risk factor for psychiatric disorders, it is not surprising that cortisol stress reactivity has frequently been investigated in patients versus healthy individuals. However, the large heterogeneity in measures of the cortisol stress response has hampered a systematic evaluation of the evidence. We here report of a systematic literature r
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376 to 400 of 897Salivary alpha-amylase stress reactivity across different age groups.
tract Salivary alpha-amylase (sAA) increases rapidly in response to psychosocial stress in young adults, but no direct comparisons between different age groups across the life span have been made. Secretion of sAA and cortisol was assessed in children, young adults, and older adults after exposure to the Trier Social Stress Test. Additionally, cardiovascular activity was measured in both adult groups. Older adults showed attenuated sAA, heart rate (HR), and heart rate variability (HRV) responses. Furthermore, we found higher sAA but lower cortisol at baseline as well as lower sAA and cortisol responses in children. Age x sex interactions were observed only for cortisol with higher responses in older male participants. No associations between the parameters were found. These results implicate sAA as an alternative or additional sympathetic stress marker throughout the life span, with mark…
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Modeling multisystem biological risk in young adults: The Coronary Artery Risk Development in Young Adults Study.
Although much prior research has focused on identifying the roles of major regulatory systems in health risks, the concept of allostatic load (AL) focuses on the importance of a more multisystems view of health risks. How best to operationalize allostatic load, however, remains the subject of some debate. We sought to test a hypothesized metafactor model of allostatic load composed of a number of biological system factors, and to investigate model invariance across sex and ethnicity. Biological data from 782 men and women, aged 32-47, from the Oakland, CA and Chicago, IL sites of the Coronary Artery Risk Development in Young Adults Study (CARDIA) were collected as part of the Year 15exam in 2000. These include measures of blood pressure, metabolic parameters (glucose, insulin, lipid profiles, and waist circumference), markers of inflammation (interleukin-6, C-reactive protein, and fibrin…
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Developmental changes in hypothalamus-pituitary-adrenal activity over the transition to adolescence: normative changes and associations with puberty.
Home baseline and laboratory stressor (Trier Social Stress Test for Children) measures of salivary cortisol were obtained from 82 participants (40 girls) aged 9, 11, 13, and 15 years. Measures of pubertal development, self-reported stress, parent reports of child depressive symptoms and fearful temperament, and cardiac measures of sympathetic and parasympathetic activity were also obtained. Significant increases in the home cortisol baselines were found with age and pubertal development. Cortisol stress reactivity differed by age group with 11-year-olds and 13-year-old boys showing blunted reactivity and 9-year-olds, 13-year-old girls, and 15-year-olds showing significant cortisol reactions. Cortisol reactivity correlated marginally with sexual maturation. Measures of sympathetic activity revealed increased sympathetic modulation with age. Higher sympathetic tone was associated with more…
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Hypothalamus-pituitary-adrenal axis hyperresponsiveness is associated with increased social avoidance behavior in social phobia.
Background: Social avoidance and inhibition in animals is associated with hyperresponsiveness of the glucocorticoid stress-system. In humans, the relation between glucocorticoid stress-reactivity and social avoidance behavior remains largely unexplored. We investigated whether increased cortisol stress-responsiveness is linked to increased social avoidance behavior in patients with social anxiety disorder (SAD). Methods: Patients with SAD (n = 18) as well as two control groups of healthy participants (n = 22) and patients with posttraumatic stress disorder (PTSD; n = 17), respectively, performed a social approach-avoidance task (AA-task) in a baseline condition and in a social stress condition (provided by the Trier Social Stress Test). The AA-task is a computerized reaction-time task measuring the speed of manual approach and avoidance responses to visually presented social threat cues …
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Cortisol inhibits neuroplasticity induction in human motor cortex.
We investigated whether plasticity of human motor cortex (M1) is influenced by time of day, and whether changes in circulating levels of cortisol contribute to this effect. Neuroplasticity was induced using paired associative stimulation (PAS), involving electrical stimulation of left median nerve, paired with transcranial magnetic stimulation over the right M1 25 ms later (90 pairs at 0.05 Hz). Surface EMG was recorded from the left abductor pollicis brevis (APB) and first dorsal interosseous muscle. Cortisol levels were assessed from saliva. Time-of-day modulation of PAS effectiveness was assessed in 25 subjects who were tested twice, at 8:00 A.M. and 8:00 P.M. on separate days. In a second double-blind study, 17 subjects were tested with PAS at 8:00 P.M. on two occasions after administration of oral hydrocortisone (24 mg) or placebo. The motor-evoked potential (MEP) in resting APB inc…
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Effects of early and recent adverse experiences on adrenal response to psychosocial stress in depressed adolescents.
Background: As observed in depressed adults, there is considerable variability in the degree and direction of hypothalamic-pituitary-adrenal (HPA) dysfunction in depressed adolescents. The variability in HPA findings may be attributed to experiential factors. Methods: A modified version of a standard psychosocial stressor used in adults, the Trier Social Stress Test (TSST), was administered to 30 adolescents with major depressive disorder and 25 healthy adolescent volunteers. Cortisol concentrations were measured in saliva samples collected before and after the stressor. Information was also gathered on early and recent adverse experiences with standard interviews. Results: Participants from both groups had increased cortisol secretion in response to TSST. Compared with control subjects, depressed subjects showed more elevated and prolonged cortisol secretion in response to TSST. The com…
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Inflammatory responses to psychological stress in fatigued breast cancer survivors: relationship to glucocorticoids.
Fatigue is a common problem following cancer treatment and our previous studies suggest that a chronic inflammatory process might contribute to cancer-related fatigue. However, immune responses to challenge have not yet been evaluated among individuals with cancer-related fatigue, and it is not known what mechanisms drive increased levels of inflammatory markers in fatigued cancer survivors. We have previously reported that fatigued breast cancer survivors show a blunted cortisol response to an experimental psychological stressor. In this report, we focus on inflammatory responses to this stressor and their relationship to circulating glucocorticoids and cellular sensitivity to glucocorticoid inhibition. Relative to non-fatigued control survivors, participants experiencing persistent fatigue showed significantly greater increases in LPS-stimulated production of IL-1beta and IL-6 followin…
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Thermoregulatory and endocrine responses to light pulses in short-day acclimated social voles (Microtus socialis).
In mammals, nocturnal light pulses (NLP) have been demonstrated to affect physiology and behavior. However, the impact of NLP as a stressor has been less broadly examined. The purpose of this study was to examine the effect of NLP (three 15 min 450 lux light pulses) during each scotophase on both thermoregulation and endocrine stress responses under short-day (SD; 8L:16D) acclimation. Voles were acclimated to either SD (SD voles) or SD+NLP (NLP voles). Resistance to cold was estimated by measurements of body temperature (T(b)) during cold exposure (5 degrees C). Daily rhythms of energy expenditure (calculated from oxygen consumption), urine production, and urinary adrenaline and serum cortisol levels were measured. T(b) values of SD voles were generally unaffected by the cold stimulus, whereas in NLP voles, resistance to cold was markedly lowered. While SD- and NLP voles showed similar u…
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Impaired memory retrieval correlates with individual differences in cortisol response but not autonomic response.
Stress can enhance or impair memory performance. Both cortisol release and sympathetic nervous system responses have been implicated in these differential effects. Here we investigated how memory retrieval might be affected by stress-induced cortisol release, independently of sympathetic nervous system stress responses. Thirty-two healthy participants (16 women) learned emotionally arousing and neutral words. One hour later, half of the participants underwent a stressor (cold pressor test) and the other half, a control warm water exposure, both followed by a delayed free recall task. The stressed participants were split into those who did (responders, N = 8) and those who did not (nonresponders, N = 6) show a cortisol response. Both responders and nonresponders showed comparable sympathetic nervous system activity (skin conductance level) during the cold pressor. The cortisol responders …
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Severe decrements in cognition function and mood induced by sleep loss, heat, dehydration, and undernutrition during simulated combat.
Background: Military exercises generate high levels of stress to simulate combat, providing a unique opportunity to examine cognitive and physiologic responses of normal humans to acute stress. Methods: Cognitive and physiologic markers of stress were evaluated before, during, and after an intense training exercise conducted for 53 hours in the heat. Cognitive performance, mood, physical activity, sleep, body composition, hydration, and saliva cortisol, testosterone, and melatonin were assessed. Volunteers were 31 male U.S. Army officers from an elite unit, aged 31.6 +/- .4 years. Results: Wrist activity monitors documented that soldiers slept only 3.0 +/- .3 hours during the exercise and were active throughout. Volunteers lost 4.1 +/- .2 kg (p < .001) of weight, predominately water (3.1 +/- .3 L) (p < .001). Substantial degradation in cognitive function, assessed with computerized tests…
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Effect of acamprosate on magnetic resonance spectroscopy measures of central glutamate in detoxified alcohol-dependent individuals: a randomized controlled experimental medicine study.
Context: Acamprosate is approved for the treatment of alcoholism, but its mechanism of action remains unclear. Results of animal studies suggest that a persistent hyperglutamatergic state contributes to the pathogenesis of alcoholism and that acamprosate may exert its actions by intervening in this process. Human translation of these findings is lacking. Objective: To examine whether acamprosate modulates indices of central glutamate levels in recently abstinent alcohol-dependent patients as measured using proton nuclear magnetic resonance spectroscopy (¹H-MRS). Design: A 4-week, double-blind, placebo-controlled, randomized controlled experimental medicine study, with ¹H-MRS measures obtained on days 4 and 25. Setting: An inpatient research unit at the NIH Clinical Center. Patients Thirty-three patients who met the DSM-IV criteria for alcohol dependence and who were admitted for medicall…
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Do workplace-based mindfulness meditation programs improve physiological indices of stress? A systematic review and meta-analysis.
Objective: Mindfulness-based interventions (MBI) have been related with improved job satisfaction, wellbeing, health, and reduced workplace stress with employees. However, until now, synthesis of the evidence of the effect of MBIs on physiological indices associated with stress and ill-health has been lacking. Therefore the current systematic review aimed to synthesise the literature from employee samples to provide guidance for future investigations in terms of which physiological indicators and biological systems may be most impacted by MBIs. Methods: Electronic databases were searched. Studies that conducted a mindfulness-based program with an employee sample, which targeted workplace stress or work engagement, and measured a physiological outcome were selected for inclusion. Studies using either a between-group or within-group design were included. Nine papers were found to meet the …
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Psychophysiological effects of walking in forests and urban built environments with disparate road traffic noise exposure: study protocol of a randomized controlled trial.
Background: Stress is a widespread phenomenon and reality of everyday life, entailing negative consequences for physical and psychological wellbeing. Previous studies have indicated that exposure to greenspaces and nature-based interventions are promising approaches to reducing stress and promoting restoration. However, an increasing percentage of the population lives in urban regions with limited opportunities to spend time in greenspaces. In addition, urban settings typically feature increased levels of noise, which represents a major environmental stressor. Although various studies have compared the effects of exposure to greenspaces versus urban built environments, evidence of the effects of noise in this context is very limited. Psychophysiological benefits of exposure to greenspaces compared to urban built environments reported in earlier studies might be less (or at least not only…
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Depressive symptoms and cortisol rhythmicity predict survival in patients with renal cell carcinoma: role of inflammatory signaling.
Purpose: Evidence has supported the association between psychological factors and cancer biology; however, findings are equivocal on the role of psychosocial factors in cancer progression. This study generates a hypothesis of mechanistic variables by examining the clinical effects of psychosocial factors and cortisol dysregulation in patients with metastatic renal cell carcinoma (RCC) and examines associated activation of transcription control pathways. Methods: Patients with metastatic RCC (n = 217) were prospectively enrolled in this study. Patients completed questionnaires (Centers for Epidemiologic Studies-Depression; SF-36 Health Status Survey; Duke Social Support Index; Coping Operations Preference Enquiry; organized and non-organized religious activity; and intrinsic religiosity), and provided blood and saliva samples. Cortisol levels and whole genome transcriptional profiling wer…
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One year pre-post intervention follow-up of psychological, immune, endocrine and blood pressure outcomes of mindfulness-based stress reduction (MBSR) in breast and prostate cancer outpatients.
Objectives: This study investigated the ongoing effects of participation in a mindfulness-based stress reduction (MBSR) program on quality of life (QL), symptoms of stress, mood and endocrine, immune and autonomic parameters in early stage breast and prostate cancer patients. Methods: Forty-nine patients with breast cancer and 10 with prostate cancer enrolled in an eight-week MBSR program that incorporated relaxation, meditation, gentle yoga and daily home practice. Demographic and health behaviors, QL, mood, stress symptoms, salivary cortisol levels, immune cell counts, intracellular cytokine production, blood pressure (BP) and heart rate (HR) were assessed pre- and post-intervention, and at 6- and 12-month follow-up. Results: Fifty-nine, 51, 47 and 41 patients were assessed pre- and post-intervention and at 6- and 12-month follow-up, respectively, although not all participants provided…
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Atrophy and impaired muscle protein synthesis during prolonged inactivity and stress.
Context: We recently demonstrated that 28-d bed rest in healthy volunteers results in a moderate loss of lean leg mass and strength. Objective: The objective of this study was to quantify changes in muscle protein kinetics, body composition, and strength during a clinical bed rest model reflecting both physical inactivity and the hormonal stress response to injury or illness. Design: Muscle protein kinetics were calculated during a primed, continuous infusion (0.08 micromol/kg.min) of 13C6-phenylalanine on d 1 and 28 of bed rest. Setting: The setting for this study was the General Clinical Research Center at the University of Texas Medical Branch. Participants: Participants were healthy male volunteers (n = 6, 28 +/- 2 yr, 84 +/- 4 kg, 178 +/- 3 cm). Intervention: During bed rest, hydrocortisone sodium succinate was administered iv (d 1 and 28) and orally (d 2-27) to reproduce plasma cor…
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Ghrelin has partial or no effect on appetite, growth hormone, prolactin, and cortisol release in patients with anorexia nervosa.
Context: Anorexia nervosa (AN) is an eating disorder characterized by self-induced starvation. Gastric hormone ghrelin, potent orexigen, and natural GH secretagogue are increased in AN. Although exogenous ghrelin stimulates appetite, GH, prolactin, and cortisol release in humans, its effects have not been studied, during infusions, in AN patients. Objective: The objective of the study was to determine the effects of ghrelin on appetite, sleepiness, and neuroendocrine responses in AN patients. Design: This was an acute interventional study. Setting: The study was based at a hospital. Investigated Subjects: Twenty-five young women, including nine patients diagnosed with AN with very low body weight, six AN patients who partially recovered their body weight but were still amenorrheic, and 10 constitutionally thin female subjects, without history of eating disorder, weight loss, with regular…
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Stressor paradigms in developmental studies: what does and does not work to produce mean increases in salivary cortisol.
The stress response system is comprised of an intricate interconnected network that includes the hypothalamic-pituitary-adrenocortical (HPA) axis. The HPA axis maintains the organism's capacity to respond to acute and prolonged stressors and is a focus of research on the sequelae of stress. Human studies of the HPA system have been facilitated enormously by the development of salivary assays which measure cortisol, the steroid end-product of the HPA axis. The use of salivary cortisol is prevalent in child development stress research. However, in order to measure children's acute cortisol reactivity to circumscribed stressors, researchers must put children in stressful situations which produce elevated levels of cortisol. Unfortunately, many studies on the cortisol stress response in children use paradigms that fail to produce mean elevations in cortisol. This paper reviews stressor parad…
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High dose hydrocortisone immediately after trauma may alter the trajectory of PTSD: interplay between clinical and animal studies.
High-dose corticosteroids have been reported to reduce symptoms of acute stress and post-traumatic stress in polytrauma patients and in animal studies. The underlying mechanism of action remains largely unclear. These issues were addressed in parallel in the clinical and preclinical studies below. In this preliminary study, 25 patients with acute stress symptoms were administered a single intravenous bolus of high-dose hydrocortisone (100-140 mg) or placebo within 6 h of a traumatic event in a prospective, randomized, double-blind, placebo-controlled pilot study. Early single high-dose hydrocortisone intervention attenuated the core symptoms of both the acute stress and of subsequent PTSD in patients. High-dose hydrocortisone treatment given in the first few hours after a traumatic experience was associated with significant favorable changes in the trajectory of exposure to trauma, as ex…
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Pharmacological REM sleep suppression paradoxically improves rather than impairs skill memory.
Rapid eye movement (REM) sleep has been considered important for consolidation of memories, particularly of skills. Contrary to expectations, we found that REM sleep suppression by administration of selective serotonin or norepinephrine re-uptake inhibitors after training did not impair consolidation of skills or word-pairs in healthy men but rather enhanced gains in finger tapping accuracy together with sleep spindles. Our results indicate that REM sleep as a unitary phenomenon is not required for skill-memory consolidation.
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Lower methylation of glucocorticoid receptor gene promoter 1F in peripheral blood of veterans with posttraumatic stress disorder.
Background: Enhanced glucocorticoid receptor (GR) sensitivity is present in people with posttraumatic stress disorder (PTSD), but the molecular mechanisms of GR sensitivity are not understood. Epigenetic factors have emerged as one potential mechanism that account for how trauma exposure leads to sustained PTSD symptoms given that PTSD develops in only a subset of trauma survivors. Methods: Cytosine methylation of a relevant promoter of the GR gene (NR3C1-1F promoter) and three functional neuroendocrine markers of hypothalamic-pituitary-adrenal axis function were examined in a sample of 122 combat veterans. Results: Lower NR3C1-1F promoter methylation in peripheral blood mononuclear cells (PBMCs) was observed in combat veterans with PTSD compared with combat-exposed veterans who did not develop PTSD. NR3C1-1F promoter methylation was also associated with three functional measures of gluc…
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Poor sleep and altered hypothalamic-pituitary-adrenocortical and sympatho-adrenal-medullary system activity in children.
Context: Neuroendocrine alterations, with well-known links with health, may offer insight into why poor sleep is associated with poor health. Yet, studies testing associations between sleep and neuroendocrine activity in children are scarce. Objective: The aim of this study was to determine whether actigraphy-based sleep pattern is associated with hypothalamic-pituitary-adrenocortical axis and sympatho-adrenal-medullary system activity in children. Design and setting: We conducted a cross-sectional study in a birth cohort in Helsinki, Finland. Participants: We studied 282 8-yr-old children. Main outcome measures: We measured diurnal salivary cortisol and salivary cortisol and alpha-amylase (a sympatho-adrenal-medullary system marker) responses to the Trier Social Stress Test for Children (TSST-C). Results: Children with short (<or=7.7 h) vs. average sleep duration (7.8-9.3 h) displayed h…
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Moderate versus severe early life stress: associations with stress reactivity and regulation in 10-12-year-old children.
Early life stress (ELS) is expected to increase reactivity of the hypothalamic-pituitary-adrenocortical (HPA) axis; however, several recent studies have shown diminished cortisol reactivity among adults and children with ELS exposure. The goal of this study was to examine cortisol activity in 10-12-year-old internationally adopted children to determine if moderate and severe ELS have different impacts on the HPA axis. Salivary cortisol and two measures of autonomic activity were collected in response to the Trier Social Stress Test for Children (TSST-C). Three groups reflecting moderate, severe, and little ELS were studied: early adopted children who came predominantly from foster care overseas (early adopted/foster care (EA/FC), n=44), later adopted children cared for predominantly in orphanages overseas (late adopted/post-institutionalized (LA/PI), n=42) and non-adopted (NA) children r…
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The contribution of hypothalamic neuroendocrine, neuroplastic and neuroinflammatory processes to lipopolysaccharide-induced depressive-like behaviour in female and male rats: Involvement of glucocorticoid receptor and C/EBP-β.
Peripheral inflammation induced by lipopolysaccharide (LPS) causes behavioural changes indicative for depression. The possible mechanisms involve the interference with neuroinflammatory, neuroendocrine, and neurotrophic processes. Apart from heterogeneity in the molecular background, sexual context may be another factor relevant to the manifestation of mood disturbances upon an immune challenge. We investigated sex-dependent effects of a 7-day LPS treatment of adult Wistar rats on depressive-like behaviour and their relation with hypothalamic neuroendocrine factor, corticotrophin-releasing hormone (CRH), proplastic brain-derived neurotropic factor (BDNF), pro-inflammatory cyclooxygenase-2 (COX-2) and nuclear factor kappa beta (NFkB). Also, their regulators, the glucocorticoid receptor (GR) and CCAAT enhancer-binding protein (C/EBP) β were followed. LPS induced depressive-like behaviour i…
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Absence of the gut microbiota enhances anxiety-like behavior and neuroendocrine response to acute stress in rats.
Background and aims: Establishment of the gut microbiota is one of the most important events in early life and emerging evidence indicates that the gut microbiota influences several aspects of brain functioning, including reactivity to stress. To better understand how the gut microbiota contributes to a vulnerability to the stress-related psychiatric disorders, we investigated the relationship between the gut microbiota, anxiety-like behavior and HPA axis activity in stress-sensitive rodents. We also analyzed the monoamine neurotransmitters in the brain upper structures involved in the regulation of stress and anxiety. Methods: Germfree (GF) and specific pathogen free (SPF) F344 male rats were first subjected to neurological tests to rule out sensorimotor impairments as confounding factors. Then, we examined the behavior responses of rats to social interaction and open-field tests. Serum…
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