Psychogenic Stress Research Articles

The effect of acute mental stress on the exchange of monoamines in the mesocortical and nigrostriatal systems of the rat brain

Background. Мesocortical and nigrostriatal dopaminergic systems are highly sensitive to stressful events. One of the most adequate models of acute psychogenic stress in animals is the death of a partner upon presentation of a predator.
 Aim. To study the content of dopamine (DA), serotonin and their metabolites: dioxyphenylacetic (DOPAC), homovanillic and 5-hydroxyindoleacetic (5-HIAA) acids in the prefrontal cortex, striatum, and ventral tegmental area in rats on days 3, 7, and 14 after the acute psychogenic stress of the death of a partner upon presentation of a predator.
 Materials and methods. 28 male Wistar rats were studied. Acute single psychotraumatic situation was used. A group of rats was placed in a tiger python terrarium. One animal died as a result of its nutritional needs, the rest of the rats experienced the death of a partner. The content of monoamines in the brain structures was carried out by high performance liquid chromatography with electrochemical detection.
 Results. Changes in the content of monoamines in the prefrontal cortex, striatum, and ventral tegmental area were found on the 7 and 14 days after the presentation of the predator. In the ventral tegmental area on the 7 day, there was an increase in the DOPAC/DA ratio and an increase in the serotonin metabolite 5-HIAA, which reflects an increase in the activity of dopamine and serotonin. In the prefrontal cortex on the 14 day, the DOPAС content and the DOPAС/DA index decreased. The 5-HIAA content in the prefrontal cortex and the 5-HIAA/5-HT value also significantly decreased.
 Conclusions. Changes in the metabolism of monoamines after presentation of a predator develop gradually: increase of the dopamine and serotonin activity in the ventral tegmental area was noted on the 7 day after presentation of the predator, decrease in their activity in the striatum and prefrontal cortex only on the 14 day, reflecting the development of depressive states and post-traumatic stress disorder.

Assessment of vitamin D level in women with abnormal uterine bleeding and chronic psychogenic stress

The objective: to study the level of vitamin D (25-hydroxycalciferol – (25(OH)D) in blood serum of women with abnormal uterine bleeding (AUB) and chronic psychogenic stress.Materials and methods. We examined 100 women of reproductive age with AUB and chronic psychogenic stress (basic group) and 50 patients with AUB without psychogenic chronic stress (comparison group). 30 women without AUB and chronic stress were included in the control group. AUB was diagnosis according to the Order No. 353 of the Ministry of Health of Ukraine dated April 13, 2016. The concentration of vitamin D was determined in blood serum in all the women using the ELISA method.Results. The concentration of vitamin D in the blood serum in patients with AUB and chronic psychogenic stress was on 28.01 % lower compared to the controls (p < 0.001), in the patients with AUB without psychogenic chronic stress – 13.94 % (p = 0.045). The number of individuals with optimal concentration of vitamin D in the control group (36.67 %) was in 2.29 times higher compared to the basic group (16.00 %; p=0.03) and in 1.41 times more compared to the comparison group (26.00 %). Suboptimal level of vitamin D had 53.33 % women in the control group, 43.00 % – basic and 58.00 % – comparison one. The rate of persons with deficiency of vitamin D among the patients with AUB and chronic psychogenic stress was in 4.56 times higher compared to the healthy women (41.00 % and 9.00 % individuals, respectively; p = 0.003), and in patients with AUB without chronic stress –1.78 time (16.00 % women).Conclusions. There is the insufficient vitamin D concentration in women with abnormal uterine bleeding which is more severe in the persons with chronic psychogenic stress.

Analisis Faktor yang Berhubungan dengan Hipertensi pada Remaja

ABSTRACT Hypertension is the cardiovascular disease that contribute to at least 45% of deaths from heart disease, and 51% of deaths from stroke. Adolescents with high blood pressure have a high risk of becoming hypertensive during adulthood. Objective: This study was aimed to investigate factors correlating with hypertension in adolescent. Methods: This study design was correlational with cross-sectional approach. The number of respondents was 125 people selected by simple random sampling technique. The independent variable of this research is gender, family history, BMI (Body Mass Index), sodium intake, smoking, psychogenic stress, parental income, and physical activity. The dependent variable of this research is hypertension. Data were taken through questionnaires, measurement of blood pressure, weight, and height and data analyzed using Spearman Correlation and Chi-Square test with α<0,05. Results: The results showed a majority of respondents aged 16 (76,8%). The results of statistical tests indicate that there are correlation between BMI (p=0,000; r= 0,355), and physical activity (p=0,047; r= -0,178 ) with hypertension in adolescent. Gender (p=0,281), family history (p=0,792), sodium intake (p=0,152), smoking (p=0,698), psychogenic stress (p=0,345), and parental income (p=0,945) not related to hypertension in adolescent. Conclusion : This research shows the majority of hypertension in adolescent into category normal, and the factors most associated is BMI. Further studies are expected to conduct research or to other factors and other research designs associated with hypertension in adolescent. Keywords: adolescent; hypertension; risk factor

Study of the anxiolytic effect of propranolol and dextromethorphan in mice using a model of psychogenic stress

Abstract Objective: To find the anxiolytic effects in a psychogenic stress model in mice, the present study has investigated the interaction between propranolol and dextromethorphan. Methods: 50 Albino Swiss male mice were housed in groups of 10 per cage. The beta-adrenergic receptor blocker propranolol (20 mg/kg bw), the N-methyl-D-aspartate (NMDA) receptor dextromethorphan (30 mg/kg bw), and their combination were administered 10 minutes after exposure to predator odor. The treatments included diazepam as positive control and normal saline as negative control. Anxiety-like behaviors were evaluated using the elevated plus-maze test (EPM) 7 days after stress induction. Results: Regarding the length of stay (F=25.53; p&lt;0.0001)/number of entries in the open arms (F=3.533; p=0.0416), time (F=6.127; p=0.0045)/number of entries in the closed arms (F=5.690; p=0.0141), time in center-point (F=3.577; p=0,0295), and total distance traveled (F= 4.711; p=0.0145), there was a significant difference among the treated groups. Propranolol and dextromethorphan treated groups expressed lower time in the closed arms vs Placebo (p=0.0089, respectively p=0.0111). In addition, the time spent in the open arms was higher in propranolol group vs placebo group (p=0.0215). Conclusions: Considering obtained data, there was a decrease of symptoms in the sympathetic nervous system and the psychological stress disappeared in mice applying a treatment of 20 mg/kg bw propranolol. Our findings indicated that dextromethorphan partially mediated the anxiolytic-like activity. However, the combination of these two drugs did not express anxiolytic effects.

Reactive changes of gastric mucosa and reduction of desacyl grelin in rat brain due to psychoemotional stress

BACKGROUND: The work is devoted to the analysis of the elements the reactivity of grelin system in the model of psychogenic stress. In recent years, it has been shown that the ghrelin brain system is not limited only to the regulation of energy balance and eating behavior. Along with other peptide regulatory systems, it plays an important role in the mechanisms of stress, reward and addiction. Therefore, the elements of this system should be considered primarily as molecular targets of pharmacological action in order to correct the states of addiction and post-stress disorders.&#x0D; MATERIALS AND METHODS: To produce psychoemotional stress, we used an acute single traumatic situation in male Wistar rats. The animals were placed in the tiger python, one animal died as a result of its nutritional needs, the rest of the rats experienced the death of a partner. One week after exposure to python, the animals were decapitated, and the brain structures were isolated. Aliquots of the brain structures suspensions were examined for the content of desacyl ghrelin (DAG) using a highly sensitive enzyme-linked immunosorbent assay (ELISA). In another group, rats were decapitated on the 4th day after exposure to python, stomachs were removed, which were fixed in 10% formalin solution. In horizontal paraffin sections of the gastric mucosa, after staining with hematoxylin and eosin, the heights of superficial and dimple mucous cells, the height of the dimple stroma, the area of superficial, dimple mucocytes and stroma of the dimples, and the number of dead mucocytes were calculated. To clarify the differentiation of epithelial cells, they were stained with alcian blue&#x0D; RESULTS: DAG was detected in all studied brain structures: amygdala, hippocampus, and hypothalamus. The highest concentration of DAG was noted in the hypothalamus (p 0.05), which may serve as an indirect confirmation of the data on the presence of ghrelin-containing neurons in the nuclei of the hypothalamus. After exposure to stress, a sharp decrease in the level of DAG was observed in all studied brain structures (812 times, p 0.01): amygdala, hippocampus, and hypothalamus. It has been established that the experience of the stress of the death of a partner is expressed by erosive inflammation of the gastric mucosa, the death of many mucous cells, and an increase in mucus production in viable epithelial cells.&#x0D; CONCLUSION: Psychoemotional stress completely suppresses the content of desacyl ghrelin of the brain in rats, which may be based on both a disturbance of the central mechanisms of limbic regulation and a violation of peripheral mechanisms, in particular, reactive changes in the gastric mucosa.

Effects of psychogenic stress on some peripheral and central inflammatory markers in rats with the different level of excitability of the nervous system.

Patients with post-stress pathologies display the signs of inflammation in the peripheral blood as well as in the brain. The mechanisms of such post-stress neuroimmune changes, their contribution to the behavior, the relationship of the intensity of inflammation with genetically determined features have not been clarified. The goal of this work was to evaluate the dynamics of post-stress inflammation in the blood and hippocampus of rats which differ in level of excitability of the nervous system. Rats of two strains (high/low excitability threshold) were subjected to stress according to the K. Hecht protocol and their behavior, neutrophil:lymphocyte ratio and the number of Iba+ cells in the hippocampus were analysed 24 hours, 7 and 24 days after stress exposure. Highly excitable animals show an increase in anxiety-like behavior, in the number of neutrophils compared to lymphocytes as well as in the number of Iba1+ cells in CA1, CA3 and DG areas of the hippocampus in response to stress. Thus, hereditary high excitability of the nervous system is a possible risk factor for the development of post-stress pathologies.

The role of nucleus of the solitary tract glucagon-like peptide-1 and prolactin-releasing peptide neurons in stress: anatomy, physiology and cellular interactions.

Neuroendocrine, behavioural and autonomic responses to stressful stimuli are orchestrated by complex neural circuits. The caudal nucleus of the solitary tract (cNTS) in the dorsomedial hindbrain is uniquely positioned to integrate signals of both interoceptive and psychogenic stress. Within the cNTS, glucagon‐like peptide‐1 (GLP‐1) and prolactin‐releasing peptide (PrRP) neurons play crucial roles in organising neural responses to a broad range of stressors. In this review we discuss the anatomical and functional overlap between PrRP and GLP‐1 neurons. We outline their co‐activation in response to stressful stimuli and their importance as mediators of behavioural and physiological stress responses. Finally, we review evidence that PrRP neurons are downstream of GLP‐1 neurons and outline unexplored areas of the research field. Based on the current state‐of‐knowledge, PrRP and GLP‐1 neurons may be compelling targets in the treatment of stress‐related disorders.LINKED ARTICLESThis article is part of a themed issue on GLP1 receptor ligands (BJP 75th Anniversary). To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v179.4/issuetoc

Behavioral analysis of anxiolytic action of phenazepam in conditions of an acute psychogenic stress (predator presentation) in Danio rerio

We studied the effect of benzodiazepine anxiolytic phenazepam after the predator presentation to Danio rerio. The test of novelty was used: the fish was placed first in a beaker with a dissolved pharmacological substance (or H2O) and then into a novel tank for 6 min, where the trajectory, the path length, the number of movements to the upper part of the novel tank, the number and time of the pattern of freezing were measured. It is shown that, in response to the novelty of tank, the fish are reacted by submerging to the bottom, increasing the frizing, and reducing the number of movements to the upper half of the novel tank. After phenazepam administration, the fish were not only in the lower, but also in the upper part of the novel tank. The average path length did not change significantly in the range of doses used. The number and time of the frizing, as well as the time spent in the lower part of the novel tank, decreased more than 2 times compared to the control group of animals and showed a dose-dependent effect. The number of movements to the upper part of the novel tank for the experiment increased significantly from 1 in the control to 57 after phenazepam in a dose of 1 mg/l. At the same time, the number of movements of fish to the upper part of the novel tank significantly increased more than 2 times from 3th min of the experiment with the use of phenazepam in a dose of 1 mg/l. Predator presentation (Hypsophrys nicaraguensis) caused an increase in the number of freezing (temporary immobilization) and a decrease in the length of the trajectory of movement in the novel tank as compared with the Danio rerio control group. Phenazapam at a dose of 1 mg/l removed the effects of a predator, while exhibiting a typical effect: the number of movements to the upper part of the tank during the experiment significantly increased to 30; the time at the bottom of the tank was halved. It was concluded that the novelty stress test and the test with a predator are highly sensitive for studying anxiety-phobic reactions in Danio rerio.

A Review of Nonpharmacological Strategies in the Treatment of Relative Energy Deficiency in Sport.

Relative energy deficiency in sport (RED-S) can result in negative health and performance outcomes in both male and female athletes. The underlying etiology of RED-S is low energy availability (LEA), which occurs when there is insufficient dietary energy intake to meet exercise energy expenditure, corrected for fat-free mass, leaving inadequate energy available to ensure homeostasis and adequate energy turnover (optimize normal bodily functions to positively impact health), but also optimizing recovery, training adaptations, and performance. As such, treatment of RED-S involves increasing energy intake and/or decreasing exercise energy expenditure to address the underlying LEA. Clinically, however, the time burden and methodological errors associated with the quantification of energy intake, exercise energy expenditure, and fat-free mass to assess energy availability in free-living conditions make it difficult for the practitioner to implement in everyday practice. Furthermore, interpretation is complicated by the lack of validated energy availability thresholds, which can result in compromised health and performance outcomes in male and female athletes across various stages of maturation, ethnic races, and different types of sports. This narrative review focuses on pragmatic nonpharmacological strategies in the treatment of RED-S, featuring factors such as low carbohydrate availability, within-day prolonged periods of LEA, insufficient intake of bone-building nutrients, lack of mechanical bone stress, and/or psychogenic stress. This includes the implementation of strategies that address exacerbating factors of LEA, as well as novel treatment methods and underlying mechanisms of action, while highlighting areas of further research.

Long term effects of peripubertal stress on excitatory and inhibitory circuits in the prefrontal cortex of male and female mice

The impact of stressful events is especially important during early life, because certain cortical regions, especially the prefrontal cortex (PFC), are still developing. Consequently, aversive experiences that occur during the peripubertal period can cause long-term alterations in neural connectivity, physiology and related behaviors. Although sex influences the stress response and women are more likely to develop stress-related psychiatric disorders, knowledge about the effects of stress on females is still limited. In order to analyze the long-term effects of peripubertal stress (PPS) on the excitatory and inhibitory circuitry of the adult PFC, and whether these effects are sex-dependent, we applied an unpredictable chronic PPS protocol based on psychogenic stressors. Using two strains of transgenic mice with specific fluorescent cell reporters, we studied male and diestrus females to know how PPS affects the structure and connectivity of parvalbumin expressing (PV+) interneurons and pyramidal neurons. We also studied the expression of molecules related to excitatory and inhibitory neurotransmission, as well as alterations in the expression of plasticity-related molecules. The structure of pyramidal neurons was differentially affected by PPS in male and female mice: while the former had a decreased dendritic spine density, the latter displayed an increase in this parameter. PPS affected the density of puncta expressing excitatory and inhibitory synaptic markers exclusively in the female mPFC. Similarly, only in female mice we observed an increased complexity of the dendritic tree of PV+ neurons. Regarding the perisomatic innervation on pyramidal and PV + neurons by basket cells, we found a significant increase in the density of puncta in stressed animals, with interesting differences between the sexes and the type of basket cell analyzed. Finally, the PPS protocol also altered the total number of somata expressing the polysialylated form of the neural cell adhesion molecule (PSA-NCAM) when we analyzed both sexes together. These results highlight the strong programming effects of aversive experiences during early life for the establishment of cortical circuitry and the special impact of these stressful events on females.

1-desamino-8-D-arginin-vasopressin, DDAVP, increases the content of brain-derived neurotrophic factor (BDNF) in blood plasma of rats in model of post-traumatic stress disorder

Objective. We aimed to analyze the effect of an agonist of vasopressin type 2 receptors, 1-desamino-8-D-arginine-vasopressin, DDAVP, on the content of the brain neurotrophic factor, BDNF, in the hippocampus and blood plasma of rats exposed to vital stress.&#x0D; Material and methods. The study carried out on female Wistar rats divided into 4 groups: first group included control animals, 2 those who received DDAVP intranasally in small doses (once 2 ∙ 109 g, course 20 ∙ 109 g), 3 those who exposed to the stress of a threat to life caused by the experience of the death of a partner from the actions of a tiger python, 4 those who exposed to stress and received DDAVP. BDNF concentration in samples was measured by immunohistochemical method.&#x0D; Results. An increase in the content of BDNF in blood plasma in rats exposed to acute psychogenic stress and received DDAVP therapy was revealed on the tenth day after stress. There was no effect of stress, DDAVP, or their combined effect on the BDNF content in the homogenate of hippocampal tissues.&#x0D; Conclusion. The results of this pilot study indicate that DDAVP has a modulatory effect on BDNF metabolism in rats exposed to vital stress. It is assumed that an increase in the level of neurotrophin in the blood of rats reflects the activation of compensatory processes.

A journey through psychiatry - A personal perspective.

A journey through psychiatry - A personal perspective.

Pekin ducks are motivated to access their nest site and exhibit a stress-induced hyperthermia when unable to do so

The origins of floor-laying in ducks could be low motivation for a nest, or stress related to difficulties with accessing a nest (e.g. competition). Using a behavioural demand test, we investigated if increasing the work required to access their nest impacted ducks’ behaviour and two indicators of stress: egg corticosterone concentration and elevation of core body temperature (stress-induced hyperthermia (SIH)). Twelve laying Pekin ducks previously trained in an operant push-door task were required to use a push-door to access their nest. The door was loaded with increasing weight (0–160% of individual BW, four nights per workload) and eventually blocked to prevent nest access. Before testing, temperature data loggers were implanted in the abdomen. Eggs were collected daily to measure corticosterone concentrations. Behaviour towards the push-door was quantified. Three birds were excluded from the experiment at an early stage. Five of the nine remaining birds pushed all workloads up to 160% BW and attempted to pass the blocked door, with another two birds pushing up to 80 and 140% BW. For those that pushed at all workloads (n = 5) the area under the curve (AUC) of hyperthermia was larger at workloads of 80% (P < 0.001), 120% (P < 0.01), 140% (P < 0.001), 160% (P < 0.001), and when the door was blocked (P < 0.001), compared with 0%. On the first night when the door was blocked, all five birds pushed more at the door, but no attempts were made to push on the following 3 nights, yet the AUC of hyperthermia did not differ between nights 2–4 of the blocked door, compared with the first night that the door was blocked. Increasing workload and inability to access the nest had no effect on corticosterone in egg albumen. It was concluded that laying Pekin ducks were motivated to access a nest. Although it was not possible to differentiate metabolic from psychogenic stress on the first night that nest access was denied, we suggest that the occurrence of hyperthermia on the subsequent nights was due to SIH resulting from frustration at their inability to use their preferred nest. Floor-laying therefore is unlikely due solely to low nest-seeking motivation. Egg corticosterone was not a relevant indicator of acute stress. Strategies to improve nest availability (e.g. decreasing competition) could improve the welfare of commercial ducks.

Oxidative stress and neuroinflammation in a rat model of co-morbid obesity and psychogenic stress

BackgroundThere is growing recognition for a reciprocal, bidirectional link between anxiety disorders and obesity. Although the mechanisms linking obesity and anxiety remain speculative, this bidirectionality suggests shared pathophysiological processes. Neuroinflammation and oxidative damage are implicated in both pathological anxiety and obesity. This study investigates the relative contribution of comorbid diet-induced obesity and stress-induced anxiety to neuroinflammation and oxidative stress. MethodsThirty-six (36) male Lewis rats were divided into four groups based on diet type and stress exposure: 1) control diet unexposed (CDU) and 2) exposed (CDE), 3) Western-like high-saturated fat diet unexposed (WDU) and 4) exposed (WDE). Neurobehavioral tests were performed to assess anxiety-like behaviors. The catalytic concentrations of glutathione peroxidase and reductase were measured from plasma samples, and neuroinflammatory/oxidative stress biomarkers were measured from brain samples using Western blot. Correlations between behavioral phenotypes and biomarkers were assessed with Pearson's correlation procedures. ResultsWe found that WDE rats exhibited markedly increased levels of glial fibrillary acidic protein (185 %), catalase protein (215 %), and glutathione reductase (GSHR) enzymatic activity (418 %) relative to CDU rats. Interestingly, the brain protein levels of glutathione peroxidase (GPx) and catalase were positively associated with body weight and behavioral indices of anxiety. ConclusionsTogether, our results support a role for neuroinflammation and oxidative stress in heightened emotional reactivity to obesogenic environments and psychogenic stress. Uncovering adaptive responses to obesogenic environments characterized by high access to high-saturated fat/high-sugar diets and toxic stress has the potential to strongly impact how we treat psychiatric disorders in at-risk populations.

Is ECLIA Serum Cortisol Concentration Measurement, an Accurate Indicator of Pain Severity in Dogs with Locomotor Pain?

Simple SummarySerum cortisol level reflects the activity of stress axis, ethological alterations, acute and chronic pain, life quality, or psychogenic stress. Although it is stated that stress can produce a measurable influence on the cortisol level, a certified value of this pain biomarker in dogs was not generally accepted yet. This interdisciplinary research emerged from the need for information in this field since not many studies were focused mainly on comparative analysis. We consider this field as a hot topic with various possible applications. Our survey is a methodological study within the fields of behavior and veterinary sciences, being relevant for the dog’s pain assessment. Results are having the guarantee of the high standard analysis of serum specimens, and using the updated Cortisol assay, with serum cortisol determined by Electrochemiluminescence immunoassay. We consider that our work could refresh the information in this field. Yet, an area of interest, specific pathology and pain particularities in a dog, being studied more and more in the last decade. What we can say is that serum cortisol limits cannot be adopted as a single and accurate pain marker in dog species, our study confirming these values, as non-conclusive for the assessment of the real pain levels in the dogs.The purpose of determining serum cortisol level is to reflect the activity of stress axis, ethological alterations, acute and chronic pain, life quality, or psychogenic stress. Although it is stated that stress can produce a measurable influence on the cortisol level, a certified value of this pain biomarker in dogs was not generally accepted yet. This study aimed to investigate if serum cortisol measured follows allopathic treatments only, or it is associated with physiotherapy, point out pain level in dogs with orthopedic disease, which could reveal the healing progress. The diagnostic identified: hip dysplasia, cranial cruciate ligament rupture, or intervertebral disc disease. Ortolani and Barden tests, together with clinical examination, drawer sign, and tibia compression test, were done in dogs exhibiting postures, and motion alteration, and X-Ray confirmed. A total of 30 dogs were grouped in healthy (n = 10) and pain groups (n = 20), the blood sampling is done at the beginning of the investigation, and after ten days of the study. Dogs were handled in two ways: G1—treated with Nonsteroidal Anti-Inflammatory Drugs (NSAIDs) only and respectively, G2—by therapy and physiotherapy. The analysis was performed on a Roche Cobas Analyzer (Roche, USA), serum cortisol being determined by Electrochemiluminescence immunoassay (ECLIA), and statistics using ANOVA, following Tukey’s Multiple Comparison Test. The results revealed that, out of ten specimens in the Control group, nine were within the normal limits: 5–65 ng × mL−1 (24.76 ± 19.48678), and one sample under the set limit. In G1, it was observed that the plasmatic P1 values were below the levels of P2, in six situations. In G2, although the status of all subjects improved radically with the removal or evident reduction of pain, confirmed clinically and imagistically, the P2 values in five dogs were higher than the initial P1 values, and in contradiction with the observed clinical reality. Comparing results, the mean difference in G1 was 0.41, and in G2 = 2.54, with an SD for G1 = 13.38, and G2 = 16.66, registering moderate development. Standard deviation illustrated that the values of treated groups were highly spread throughout the interval, and the serum cortisol assay did not generate significant statistical differences between groups in our case. This inferred the doubt whether the used detection method or values registered correctly indicates the pain levels in dog species.

A single ovarian stimulation, as performed in assisted reproductive technologies, can modulate the anxiety-like behavior and neuronal activation in stress-related brain areas in rats

Infertility affects about 8 to 12% of couples of childbearing age around the world, and is recognized as a global public health issue by the WHO. From a psychosocial perspective, infertile individuals experience intense psychological distress, related to emotional disorders, which have repercussions on marital and social relationships. The symptoms persist even after seeking specialized treatment, such as assisted reproductive technologies (ART). While the stress impact of ART outcome has been comprehensively studied, the role of supraphysiological concentrations of gonadal hormones on stress response, remains to be elucidated. This study aimed to evaluate the effect of a single ovarian stimulation on the stress response in rats. To mimic the context of ART in rodents, female rats were submitted to the superovulation (150 UI/kg of PMSG and 75 UI/kg of hCG) and then to psychogenic stress (restraint stress for 30 min/day, repeated for three days). Anxiety-like behavior was evaluated in the elevated plus-maze, and neuronal activation in the stress-related brain areas assessed by Fos protein immunoreactivity. Corticosterone, estradiol, progesterone and corpora lutea were quantified. Data were analyzed using Generalized Linear Model (GzLM). Our findings indicate anxiolytic-like and protective effects of supraphysiological concentrations of gonadal hormones induced by a single ovarian stimulation on stress response. An activation of hypothalamus-pituitary-adrenal response inhibitory pathways, with participation of the prefrontal cortex, basomedial amygdala, lateral septum, medial preoptic area, dorsomedial and paraventricular hypothalamus, was detected.

Lipid spectrum in rat offspring in a model of preconditioning of psychotraumatic effects

Psychogenic stress leads to post-traumatic stress disorders, causing gross behavioral disorders and a change in the lipid spectrum of blood serum and liver, both in individuals and their offspring. Preliminary sound loading increases the stability of rats during the experience of subsequent vital stress, which is reflected in the behavior of animals and in metabolic processes. Since preconditioning with stress music changes the state of mothers, this can affect the offspring. We have shown that stress music sessions in female rats affect the lipid parameters of their offspring. In rat pups, in comparison with the norm, the level of triglycerides in the liver tissues is increased. But the change in the lipid spectrum, both in the blood and in the liver tissues, is significantly lower than in the offspring of rats after vital stress. After sessions of stress music, rat offspring revealed gender differences: changes in lipid metabolism are more recorded in males.

SAT-008 Do Psychological Factors Influence Exercise Related Amenorrhea?

Purpose: The etiology of functional hypothalamic amenorrhea (FHA) can involve both metabolic and psychogenic stressors. The role of metabolic stress has been described in exercising women who develop FHA secondary to chronic energy deficiency attributable to inadequate dietary intake in the face of exercise training. The potential for psychological factors to contribute to exercise-related FHA is unknown. Methods: In our cross-sectional comparison of exercising women ((n=61), exercise ≥2 hours/week, age 18-35 years, BMI 16-25 kg/m2, we tested whether psychological factors discriminated participants who were deemed eumenorrheic or had FHA as confirmed by physical examination, health history, metabolic and endocrine screening, menstrual calendars and daily urinary collection for reproductive hormone metabolites. Body composition, energy balance, and metabolic and endocrine parameters were assessed in addition to psychological factors (Dysfunctional Attitudes Scale, Brief-Resilient Coping, Daily Stress Inventory, Perceived Stress Scale (PSS), Profile of Mood States (POMS), Beck Depression Inventory) and eating behaviors (Eating Disorder Inventory-2, Three-Factor Eating Questionnaire). Results: Exercising women with FHA had a significantly lower BMI (20.2 vs 21.5 m/kg2, p<0.05), less body fat (22.8 vs 25.8%, p<0.05), and a lower fat mass (56.2 vs 58.3 kg, p<0.05), compared to eumenorrheic women. Fasting total triiodothyronine (75.4 vs 89.8 ng/dL, p<0.001), leptin (5.2 vs 9.0 ng/dL, p<0.01), and the ratio of actual to predicted resting metabolic rate (0.84 vs 0.92, p<0.01) were significantly lower in FHA women. FHA women demonstrated a greater drive for thinness (2.9 vs 2.1, p<0.05), greater dietary cognitive restraint (11.3 vs 7.4, p<0.001), and displayed more dysfunctional attitudes, i.e., need for social approval (39.1 vs 33.7, p<0.05) compared to eumenorrheic women but there were no differences in perceived stress, depression, mood states, brief resilient coping, or daily stress (p >0.05). Notably, FHA women displayed a significant positive correlation between need for social approval and indicators of stress (PSS: r=0.50), depression (Beck: r=0.59), and mood (POMS-depression/dejection: r=0.55), which was not apparent in eumenorrheic women. Additionally, EDI-drive for thinness was significantly positively correlated with many of the variables associated with stress (PSS: r=0.47), depression (Beck: r=0.51), dysfunctional attitudes (r=0.55), and mood disorders (POMS-depression-dejection: r= 0.37; tension/anxiety: r=0.44)(all p<0.05). Conclusion: In exercising women, psychological factors do not overtly discriminate reproductive status; however, in women with FHA, there appears to be a higher need for social approval and restrictive eating behaviors may be related to underlying indicators of psychological stress and depression.US DoD PR054531

Cortisol Mediated ET‐1 Production During Stress: Potential Link to Cardiovascular Disease

Cardiovascular disease (CVD) is the leading cause of death and disability worldwide. Stress is a major risk factor for CVD. However, little is known about how stress leads to pathological changes over time, contributing to the development and progression of CVD. Enhancing our understanding of the molecular and cellular mechanisms that are affected following the activation of the hypothalamic‐pituitary‐adrenal (HPA) axis may provide mechanistic links connecting stress and CVD risk. Endothelin‐1 (ET‐1) is one of the most potent vasoconstrictors and it is produced by vascular endothelial cells. Recent evidence indicates that its expression is elevated following stress. However, how ET‐1 expression increases following stress is unknown. This study investigated molecular links connecting stress‐responsive hormonal signals to ET‐1 expression in endothelial cells. We found elevated ET‐1 mRNA and protein levels in heart tissue from Lewis rats exposed to mild psychogenic stressor (1.9 fold ± 0.7 relative to unexposed controls, p&lt;0.05, n=12 rats/group). ET‐1 expression and corticosterone levels were significantly correlated in rats exposed to mild psychogenic stress (r = 0.4770, p &lt; 0.0129; n=12). In vitro studies using the human endothelial cell line EA.hy926 revealed that hydrocortisone significantly increased ET‐1protein levels in a dose response manner (1.8 fold ± 0.4 relative to vehicle treatment, p&lt;0.01,n=4). We found that this effect was abolished when cells were pre‐treated with the glucocorticoid receptor (GR) antagonist mifepristone (p&lt;0.0001). Furthermore, FKBP5 gene knockdown experiments demonstrated that FKBP5 is essential for the production of ET‐1 following GR activation. Our data identifies a novel pathway for GR‐mediated ET‐1 induction, which may provide fundamental understanding of the mechanistic links connecting stress and CVD.Support or Funding InformationThis study was partly supported by the NIH (P20MD006988 and 2R25 GM060507), the Loma Linda University School of Medicine Seed Grant, GRASP Funds to JDF and by the Abbvie Research Fellowship 34254.EA‐hy926 cells exhibited increased (A) FKBP5 and (B) Edn mRNA levels in a hydrocortisone dose‐specific manner. One‐way ANOVA: relative to control: p&lt;0.05, p&lt;0.01, p&lt;0.001, p&lt;0.0001; n=4. (C‐D) We study 10nM and 100nM of hydrocortisone exposure EA‐hy926 cells for 24 hours with and without Mifepristone. This attenuates hydrocortisone effects on FKBP5 (C) and Edn (D) mRNA levels. Two‐way ANOVA: p&lt;0.05, p&lt;0.01, p&lt;0.001, p&lt;0.0001; n=4. (E) Mifepristone reduces ET‐1 protein levels in EA‐hy926 cells.Figure 1FKBP5 is required for the induction of endothelin 1 expression by cortisol. (A) FKBP5 mRNA levels were markedly reduced by FKBP5 siRNA treatment. (B) FKBP5 siRNA treatment blunted the induction of Edn by cortisol. (C) FKBP5 siRNA treatment reduced ET‐1 levels even in the presence high hydrocortisone levels. Two‐way ANOVA: p&lt;0.05, p&lt;0.01, p&lt;0.001, p&lt;0.0001; n=4.Figure 2

Neuroanatomical characterization of angiotensin‐sensitive neurons within the paraventricular nucleus of the hypothalamus reveals an access point for controlling behavioral and physiological responses to stress.

Stressors perceived in the environment or those arising from the internal milieu create neural signals that converge on the paraventricular nucleus of the hypothalamus (PVN). The PVN contains distinct neuronal phenotypes that integrate and transduce these signals into cardiovascular, neuroendocrine and behavioral responses that cope with the impact of psychological and physiological stress. Accumulating evidence implicates angiotensin receptors within the PVN as mediators of the stress response; however, the neuroanatomical mechanisms underlying these effects are not completely understood. Here, we use the Cre‐LoxP system in mice with virally‐mediated gene transfer and optogenetics to characterize the structure and function of neurons in the PVN that express the angiotensin type 1a receptor (Agtr1a). Neuroanatomical experiments discovered that Agtr1a(s) were expressed on neurons in the PVN that synthesize mRNAs for corticotropin‐releasing‐hormone (CRH) or thyroid‐releasing‐hormone (TRH). These CRH and TRH neurons were found to send direct axonal projections to the median eminence and their optogenetic excitation increased, but inhibition decreased, circulating levels of corticosterone and thyroxine, indicating that Agtr1a‐expressing neurons in the PVN control the activity of neuroendocrine axes. To investigate how angiotensin signaling may affect stress responding, we engineered mice with Agtr1a specifically deleted from the PVN (Agtr1a‐PVN KO). Under basal conditions, no effect of the deletion was observed; however, maintenance on high fat diet, a metabolic stressor, revealed a gene x environment interaction whereby Agtr1a‐PVN KO mice had increased adiposity and body weight but lower blood pressure relative to controls. In psychogenic stress paradigms, Agtr1a‐PVN KO mice were found to have slight but significant decreases in anxiety‐like behavior and cardiovascular reactivity. Collectively, these results suggest that stimulation of Agtr1a(s) in the PVN contribute to activation of neuroendocrine axes that mediate behavioral and physiological responses to metabolic and psychogenic stressors.Support or Funding InformationNIH: HL122494, HL139868, HL136595