Post-stress Period Research Articles

Assessment of heat stress in 7-week old dairy calves with non-invasive physiological parameters in different thermal environments.

We estimated thermal stress in 7-week old Holstein bull calves during a warm episode in summer to study acute physiological responses of calves to heat stress. Data were collected over a 5-day period: day 1 (control), day 2 (heat stress), and a 3-day post-stress period in shaded (n = 8) and unshaded (n = 8) thermal environments. On the control day, both groups were shaded. Thermal environment was characterized by relative humidity, ambient temperature, and the temperature–humidity index (THI). Physiological variables included respiratory rate, rectal temperature, ear skin temperature and heart rate. Correlations between animal-based and meteorological indices were calculated, and ambient temperature correlated slightly better with physiological measures than THI. Rectal temperature was the only animal-based parameter that showed stronger correlations with the thermal indices when calculated for the shaded than for the unshaded environment [r = 0.42 vs. r = 0.47, P = 0.032 (ambient temperature), r = –0.39 vs. r = –0.45, P = 0.012 P = 0.015 (relative humidity), r = 0.41 vs. r = 0.46, P = 0.022 (THI)]. No differences were found between groups during the control day for any of the physiological parameters. During days 2 and 3, average and maximal values of respiratory and heart rates were higher in unshaded calves than in shaded ones. Maximal respiratory rates were in average by 25.9, 17.8 and 10.1 breaths/min lower in shaded calves than in unshaded calves for days 2, 3 and 4, respectively (P < 0.001, P < 0.001 and P = 0.024). Maximal heart rate was 127.4 ± 8.5 vs. 99.2 ± 6.3 beats/min on the heat stress day (P < 0.001), and 121.0 ± 6.9 vs. 103.4 ± 7.7 beats/min on day 3 (P = 0.006) in unshaded and shaded calves, respectively. Maximal body temperatures were higher measured either in the rectum or on the ear skin in unshaded calves than in shaded ones (with 0.5 and 1.6°C, P = 0.040 and P = 0.018, respectively), but only on the heat stress day. Based on our results, shading of young calves may be adequate for alleviating acute heat stress in continental regions. Ambient temperature is appropriate to estimate acute heat stress in dairy calves.

Association between human and animal thermal comfort indices and physiological heat stress indicators in dairy calves

Warm summer episodes have a significant effect on the overall health and well-being of young cattle; however, it is not known which temperature measure should be used for estimating heat stress in dairy calves. In this study, generalized linear mixed-effects models were used to estimate the relationships between thermal comfort indices and animal-based heat stress indicators in sixteen Holstein bull calves that were housed in individual calf hutches. Data were collected under continental weather characteristics over a 5-day period: day 1 (lower-temperature day), days 2 and 3 (heat stress days), and a 2-day post-stress period. Relative humidity, ambient temperature, the heat index, the humidex and five different temperature–humidity indices (THI) were used as thermal indices. Physiological variables monitored included respiratory rate, rectal temperature, ear skin temperature and heart rate. The heat index and the humidex measuring human thermal comfort were more closely associated with physiological measures than were the ambient temperature or the THIs (in case of heat index: R2 = 0.87 for respiratory rate, R2 = 0.63 for rectal temperature, R2 = 0.70 for ear skin temperature, and R2 = 0.78 for heart rate, respectively; in case of humidex: R2 = 0.85 for respiratory rate, R2 = 0.60 for rectal temperature, R2 = 0.68 for ear skin temperature, and R2 = 0.75 for heart rate, respectively). Based on our results, parameters of human outdoor comfort seem better to estimate heat stress in dairy calves in a continental region than those of THIs or ambient temperature.

Blood Cytokine Profile in Rats with Various Behavioral Characteristics after a Single Exposure to Long-Term Stress

Changes in the blood cytokine profile of rats with different behavioral activity were evaluated in various periods after stress exposure on the model of 24-h immobilization. Behaviorally active animals exhibited only a tendency to a change in the concentration of study cytokines in the dynamics after experimental stress. Stress exposure in passive specimens was accompanied by a decrease in the content of pro- and anti-inflammatory cytokines. These changes were most pronounced at the early stages of the post-stress period and persisted until the end of observations. After a single exposure to long-term immobilization, cytokine level in the peripheral blood of behaviorally passive animals was much lower than in active rats. Variations in immune indexes of mammals depend on the initial parameters of their behavior and duration of the post-stress period. Differences in the blood cytokine profile during negative emotiogenic exposures in passive and active rats are probably related to the specifics of immune reactivity in specimens with various sensitivities to stress.

Inhibition of BDNF signaling in the paraventricular nucleus of the hypothalamus lowers acute stress-induced pressor responses.

Brain-derived neurotrophic factor (BDNF) expression increases in the paraventricular nucleus of the hypothalamus (PVN) during stress, and our recent studies indicate that BDNF induces sympathoexcitatory and hypertensive responses when injected acutely or overexpressed chronically in the PVN. However, it remained to be investigated whether BDNF is involved in the mediation of stress-induced cardiovascular responses. Here we tested the hypothesis that inhibition of the high-affinity BDNF receptor TrkB in the PVN diminishes acute stress-induced cardiovascular responses. Male Sprague-Dawley rats were equipped with radiotelemetric transmitters for blood pressure measurement. BDNF-TrkB signaling was selectively inhibited by viral vector-mediated bilateral PVN overexpression of a dominant-negative truncated TrkB receptor (TrkB.T1, n = 7), while control animals ( n = 7) received green fluorescent protein (GFP)-expressing vector injections. Rats were subjected to acute water and restraint stress 3-4 wk after vector injections. We found that body weight, food intake, baseline mean arterial pressure (MAP), and heart rate were unaffected by TrkB.T1 overexpression. However, peak MAP increases were significantly reduced in the TrkB.T1 group compared with GFP both during water stress (GFP: 39 ± 2 mmHg, TrkB.T1: 27 ± 4 mmHg; P < 0.05) and restraint stress (GFP: 41 ± 3 mmHg, TrkB.T1: 34 ± 2 mmHg; P < 0.05). Average MAP elevations during the poststress period were also significantly reduced after both water and restraint stress in the TrkB.T1 group compared with GFP. In contrast, heart rate elevations to both stressors remained unaffected by TrkB.T1 overexpression. Our results demonstrate that activation of BDNF high-affinity TrkB receptors within the PVN is a major contributor to acute stress-induced blood pressure elevations. NEW & NOTEWORTHY We have shown that inhibition of the high-affinity brain-derived neurotrophic factor receptor TrkB in the paraventricular nucleus of the hypothalamus significantly reduces blood pressure elevations to acute stress without having a significant impact on resting blood pressure, body weight, and food intake.

Cellular Composition of the B- and T-Cell-Dependent Areas in the Small Intestine during the Post-Stress Period (Experimental Study).

A quantitative study of lymphoid cells in the B- and T-cell-dependent areas of intestinal lymphoid nodules and mesenteric lymph nodes in behaviorally passive and active rats was performed at various periods after acute stress on the model of 1-h immobilization with simultaneous electrocutaneous stimulation. Stress exposure is accompanied by a decrease in the number of lymphoid cells in immunogenic structures of the gastrointestinal tract. Post-stress changes in the cytoarchitectonics of B- and T-cell-dependent areas in mesenteric lymph nodes of animals are less pronounced than in lymphoid nodules. Quantitative changes in lymphoid cells of B-cell-dependent areas in the small intestine of rats are greater than in T-cell-dependent areas. Changes in the cellular composition of immunogenic structures in the digestive system are most significant at the early stages of the post-stress period (1st week). Passive rats are characterized by significant changes in the cytoarchitectonics of B- and Tcell-dependent areas in the small intestine after extreme exposure, which illustrates functional exhaustion of the lymphoid tissue in stress-predisposed specimens.

Effects of Intrahippocampal Injections of Melipramin on EEG, Brain Self-Stimulation, and Behavioral Indices of Rats under Conditions of Neurogenic Stress

In young (3-month-old) male Wistar rats, we studied the effects of intrahippocampal microinjections of melipramin under conditions of emotional stress induced by sessions of electrical nociceptive stimulation of the limbs. In most cases, seven-day-long stressing resulted in suppression of electrical activity of the hippocampus, exerted ambivalent effects on the frequency of brain self-stimulation (BSS) events, decreased the communicability of animals in the two-chamber test, and increased the latencies of going of the animal from the arena center and grooming episodes in the open field test. Injections of melipramin interfered with the development of stress-induced disorders in the hippocampus, decreased the normalized content of beta oscillations in the neocortex and the theta-index in the hypothalamus, increased the BSS frequency, and decreased the level of negativation of the behavioral manifestations of this phenomenon. The duration of stay of a rat near the partition in the two-chamber test increased, the mobility and number of grooming episodes in the open field enhanced, but the latency of leaving the arena center also increased (similarly to what was observed in the control). On the 8th–9th day of the poststress period, behavioral disorders of rats of the control group in the two-chamber test were smoothed to a significant extent. The stability of the examined indices or the reverse development of stress-induced disorders within the above period in animals injected with melipramin were indicative of a significant role of the hippocampus in the formation of central effects of this antidepressant and also of adaptogenic and stress-protective properties of this drug.

A gene-driven recovery mechanism: Drosophila larvae increase feeding activity for post-stress weight recovery.

Recovery from weight loss after stress is important for all organisms, although the recovery mechanisms are not fully understood. We are working to clarify these mechanisms. Here, we recorded enhanced feeding activity of Drosophila melanogaster larvae from 2 to 4h after heat stress at 35°C for 1h. During the post-stress period, expression levels of sweet taste gustatory receptor genes (Grs), Gr5a, Gr43a, Gr64a, and Gr64f, were elevated, whereas bitter taste Grs, Gr66a, and Gr33a, were decreased in expression and expression of a non-typical taste receptor Gr, Gr68a, was unchanged. Similar upregulation of Gr5a and downregulation of Gr66a was recorded after cold stress at 4°C. Expression levels of tropomyosin and ATP synthase ß subunit were significantly increased in larval mouth parts around 3 to 5h after the heat stress. We infer that up-regulation of post-stress larval feeding activity, and weight recovery, is mediated by increasing capacity for mouth part muscular movements and changes in taste sensing physiology. We propose that Drosophila larvae, and likely insects generally, express an efficient mechanism to recover from weight loss during post-stress periods.

INHIBITING GLUCOCORTICOID RECEPTOR DIMERIZATION BLOCKS EFFECTS OF ACUTE STRESS ON Aβ IN FEMALE MICE

Results from both human and animal studies over the last decade have identified a clear increase in the rate of Alzheimer's disease (AD) in women. Sex differences in the prevalence or severity of many diseases are well recognized. A common underlying feature of disorders more prevalent in females is an association with stress, such as in anxiety and depression. Stress increases glucocorticoids (GC) in the brain, and the link between GCs and AD has been confirmed by several studies. We previously found that acute stress rapidly increases levels of Aβ in the mouse brain. GCs function through a nuclear GC receptor (GR) that acts as a dimer to facilitate transactivation or as a monomer to repress transcription (transrepression). The sex-related differences in transactivation versus transrepression remain unclear and the influence of either pathway on AD pathology has not been defined. Using microdialysis, Aβ levels in the interstitial fluid (ISF) of the hippocampus were measured in male and female APP/PS1 mice (3–4 months old). Samples were collected every hour for a baseline period, 3-hour restraint stress, and 12-hour post stress period. To evaluate the effects of blocking the transactivation arm of GR signaling through GR dimerization, we crossed APP/PS1 mice with the glucocorticoid receptor dimerization deficient mouse model (GRdim), to create GRdim APP mice. We also studied the effects of pharmacologically blocking GR dimerization using Compound A, administered via reverse microdialysis before restraint stress. We observed a significant difference between male and female mice in the percent increase in ISF Aβ during acute stress, with female mice having a much greater and sustained increase in ISF Aβ compared to males. ISF Aβ levels in female GRdim APP mice did not rise dramatically during acute stress, and stayed near baseline during the post stress period. Compound A completely blocked the increase in ISF Aβ induced by restraint stress in female mice. These results suggest that females are more sensitive to stress-induced increases in Aβ, and that acute stress increases Aβ in female mice through a GR dimerization dependent mechanism.

Динамика ноцицептивной чувствительности крыс после введения мелатонина в норме и при длительном стрессорном воздействии

Цель - изучение динамики ноцицептивной чувствительности крыс в разные временные периоды после внутрибрюшинного введения мелатонина (10 мг/кг) в условиях нормы и при однократной длительной стрессорной нагрузке на модели 24-ч иммобилизации. Результаты. Установлено, что введение мелатонина приводит к усилению перцептуального компонента ноцицепции животных, выраженность которого возрастает на протяжении 8 сут. наблюдений. На 3-и - 5-е сут. у этих особей выявлено возрастание порога вокализации в ответ на электрокожное раздражение, что иллюстрирует ослабление эмоционального компонента болевой чувствительности. Стрессорное воздействие сопровождалось снижением латентного периода реакции отведения хвоста при светотермальном раздражении, что наблюдалось сразу, а также через 1, 2 и 3 сут. после окончания стрессорного воздействия. В этих условиях увеличение порога вокализации крыс при электрокожной стимуляции обнаружено сразу после стрессорной нагрузки. Указанные изменения характеризуют усиление перцептуального компонента ноцицепции - формирование гипералгезии, но подавление эмоционального восприятия болевого раздражения на ранних стадиях постстрессорного периода. Показано, что экзогенный мелатонин не предупреждает развитие гипералгезии после 24-ч иммобилизации, однако подавляет эмоциональный компонент ноцицептивной чувствительности животных в отдаленный период после длительного стрессорного воздействия (4-е и 7-е сут.). Заключение. Применение мелатонина в целях коррекции измененной болевой чувствительности, при отрицательных эмоциогенных нагрузках, необходимо проводить с учетом временной стадии постстрессорного периода, а также принимая во внимание необходимость воздействия на перцептуальный или эмоциональный компонент ноцицепции. The dynamics of nociceptive sensitivity in rats was studied in various periods after intraperitoneal injection of melatonin (10 mg/kg) under normal conditions and during long-term stress exposure on the model of 24-h immobilization. Administration of melatonin was shown to enhance the perceptual component of nociception, whose degree progressively increased over 8 days of observations. The vocalization threshold of these specimens in response to electrocutaneous stimulation was elevated on days 3-5, which illustrates suppression of the emotional component of nociceptive sensitivity. Stress exposure in animals was accompanied by a decrease in the tail-flick latency during light-heat stimulation. It was observed immediately and 1, 2, and 3 days after termination of the stress procedure. An increase in the vocalization threshold of rats was found immediately after stress. These changes illustrate an enhancement of the perceptual component of nociception (hyperalgesia), but suppression of the emotional evaluation of pain stimulation at the early stage of the post-stress period. Exogenous melatonin did not prevent the development of hyperalgesia after 24-h restraint stress. However, melatonin inhibited the emotional component of nociceptive sensitivity in animals during the late period after long-term stress exposure (days 4 and 7). We conclude that the use of melatonin for correction of changes in nociceptive sensitivity due to negative emotiogenic factors should be performed taking into account the stage of the post-stress period and necessity to affect the perceptual or emotional component of nociception.

Proteomic Characteristics of Blood Serum in Rats with Different Behavioral Parameters after Acute Stress.

We studied proteome profile of blood serum of Wistar rats with different behavioral activity immediately and in 1 and 3 days after acute stress on the model of 12-h immobilization during the nighttime. Comparative analysis of 2D-electrophoretograms revealed differences in the expression of serum proteins in non-stressed (control) and stressed (experimental) rats. We found 22 protein spots that characterized the proteomic features of blood serum in rats with different prognostic resistance to stress. Mass-spectrometry of isolated spots identified 6 functional proteins. Persistent proteome changes in the blood of animals at different stages after acute stress were determined. The specificity of proteomic characteristics of blood serum was shown in behaviorally passive and active rats during the post-stress period. These data extend the concept on specific protein markers for the formation of a negative emotional state and adaptive-and-compensatory processes in mammals with different sensitivity to stressogenic factors.

A randomized-controlled trial of heart rate variability biofeedback for psychotic symptoms

Arousal and the way it is coped with are relevant to the emergence of psychotic symptoms. Heart rate variability (HRV) stems from autonomic responses to environmental demands such as stress and is an index of physiological arousal, adaptability, and homeostatic reflexes forming autonomic balance. A randomized-controlled between-subjects trial that compared HRV-biofeedback (BF) to an active relaxation and to a waiting control condition was conducted in a sample with attenuated subclinical psychotic symptoms (N = 84). A 20-min intervention was preceded and followed by repeated assessments of stress responses. Change scores of the post-stress periods were analyzed using ANOVAs for HRV, subjective stress, perceived control, and state paranoia. As expected, BF participants showed greater improvements in perceived control than waiting controls (p = 0.006). However, no group differences occurred in HRV, paranoid symptoms or subjective stress. In exploratory analyses in a subset of participants who were breathing per protocol, the expected effects were found for total HRV and state paranoia. Thus, this trial of HRV-BF for people with attenuated psychotic symptoms indicates that the intervention may hold potential if conducted per protocol. To reach this, longer training might be inevitable. Future studies are needed to further elucidate efficacy and applicability of HRV-BF in clinical samples.

Effects of Chronic Neurogenic Stress on Behavior of Rats and Contents of Sphingolipids in Their Brain and Peripheral Tissues

We studied the contents of ceramide and sphingomyelin (SM) in the hippocampus, neocortex, and peripheral tissues of rats and the behavior characteristics of these animals in the open field at different times after the induction of chronic neurogenic stress. The experiments were carried out on young Wistar rats weighing 180–220 g, with a mean level of behavioral mobility. Within the poststress period, animals demonstrated significant suppression of manifestations of motor and orientational/research activities, and intensification of autonomic manifestations of fear and anxiety (with a delay of leaving the field center). One day after termination of stressing, the content of ceramide in the hippocampus increased against the background of a drop in the SM level, but this did not occur in the neocortex, liver, and blood serum. The contents of phosphatidylcholine and phosphatidylethanolamine in the brains of animals exposed to stress did not change. Eight days after stressing, the level of ceramide in the brain structures and blood serum was significantly higher than in the control. These data suggest that the action of chronic neurogenic stress leads to activation of metabolism of sphingolipids and intensification of production of ceramide in the brain and blood serum. Accumulation of ceramide in the serum within a remote period after termination of the action of stress can serve as a marker of the stable development of a state of emotional tension accompanied by typical signs of depression-like behavior.

Corticosterone and immune cytokine characterization following environmental manipulation in female WKY rats

This study investigated the effects of environmental manipulation on female Wistar Kyoto (WKY), an animal model of depression, and female Wistar rats. It explored the function of the hypothalamic-pituitary-adrenal axis (HPA) and immune system, as they have both been implicated in the pathophysiology of depression. A further goal was to characterize the immune cytokine concentrations of female WKY rats as this has, to our knowledge, never been documented. Animals were assigned to enriched, standard, or impoverished housing for four consecutive weeks. Following this, serum was collected at baseline and post-stress periods to measure the concentration of corticosterone, TNF-α, IL-1β, and IL-10. WKY animals had significantly higher corticosterone levels at the post-stress time-point than their Wistar counterparts. WKY females in isolation tended to have the lowest corticosterone levels which may indicate that they prefer a solitary environment, a symptom of depression. We observed a significant decrease in TNF-α after enrichment in the Wistar strain. A similar decrease in TNF-α was found in the WKY strain, but there was no difference between environmental conditions. There was a significant increase in pre- to post-stress IL-10 level in both Wistar and WKY animals. WKY females had a significantly lower level of IL-1β as compared to the Wistar animals at both pre- and post-stress time points. Given this strain difference, it is likely that the WKY rats had a dysregulated HPA axis which further influenced their circulating cytokine levels. Further studies are needed to examine how this pattern of findings plays a role in the pathophysiology of depression.

The association between openness and physiological responses to recurrent social stress

The association between openness (assessed by shortened Chinese version of NEO Five-Factor Inventory, NEOFFI) and physiological reactivity to, and recovery from, social stress (a video-recorded, timed public speaking task with evaluators present in the room), and physiological adaptation to repeated social stress was examined in the present study. Subjective and physiological data were collected from 70 college students across five laboratory stages: baseline, stress exposure period 1, post-stress period 1, stress exposure period 2, and post-stress period 2. Results indicated that higher openness was associated with lesser heart rate (HR) reactivity to the first and second stress exposure, and lesser systolic blood pressure (SBP) reactivity to the second stress exposure. Higher openness was associated with higher resting respiratory sinus arrhythmia (RSA), lesser RSA withdrawals to the first stress exposure, and more complete RSA recovery after the first stress exposure. Moreover, higher openness was associated with pronounced systolic and diastolic blood pressure (SBP, DBP) adaptation with greater decreases in SBP and DBP reactivity across the two successive stress exposures. These findings might shed light on the biological basis linking openness to health.

Salicylic acid-induced protection against cadmium toxicity in wheat plants

We have studied the influence of pretreatment of wheat seedlings (Triticum aestivum L.) with 50μM salicylic acid (SA) on plant resistance to subsequent action of 1mM cadmium acetate. SA pretreatment decreased the extent of detrimental effect of cadmium on wheat plants, as judged by the decline in the level of stress-induced accumulation of MDA and electrolyte leakage. Furthermore, SA-pretreatment contributed to maintenance of growth characteristics of wheat seedlings at the level close to the control under stress conditions and to acceleration of growth recovery during post-stress period. Detected defense effect of SA may be due to a decline in the amplitude of cadmium-induced accumulation of abscisic acid (ABA) and to reduced fall of indoleacetic acid (IAA) and cytokinins (CK) in stressed plants. In the course of one day treatment, SA activated phenylalanine ammonia-lyase (PAL), the key enzyme of lignin biosynthesis, in roots of seedlings under normal growth conditions contributing to the strengthening of carrier functions of cell walls. This assumption is supported by the data showing significant decline in cadmium accumulation in SA-pretreated plants, especially in the shoots. Cd-treatment was shown to result in accumulation of dehydrins with molecular mass 22, 28, 55 and 69kDa in wheat seedlings, although low molecular weight dehydrins (22 and 28kDa) showed greater stress sensitivity. It is noteworthy that SA-pretreatment by itself led to 1.5-fold increase in the content of low molecular weight dehydrins. Nevertheless, SA-pretreated seedlings were characterized by significantly lower Cd-induced accumulation of all of the four dehydrins, apparently due to inhibition of cadmium flow into the plants. The obtained data suggest involvement of dehydrins in the range of defense reactions induced by SA-treatment contributing significantly to development of plant resistance to subsequent action of stress. The use of fluridone allowed us to demonstrate the key role of endogenous ABA in SA-induced changes in the level of dehydrins as well as in the protective effect of SA on wheat plants under cadmium stress resulting from development of defense responses in the course of SA-treatment.

Effect of short-term weight loss on mental stress-induced cardiovascular and pro-inflammatory responses in women

Epidemiologic evidence links psychosocial stress with obesity but experimental studies examining the mechanisms that mediates the effect of stress on adiposity are scarce. The aim of this study was to investigate whether changes in adiposity following minimal weight loss affect heightened stress responses in women, and examine the role of the adipokine leptin in driving inflammatory responses. Twenty-three overweight or obese, but otherwise healthy, women (M age = 30.41 ± 8.0 years; BMI = 31.9 ± 4.1 kg/m2) completed standardized acute mental stress before and after a 9-week calorie restriction program designed to modify adiposity levels. Cardiovascular (blood pressure and heart rate) and inflammatory cytokines (leptin and interleukin-6; IL-6) responses to mental stress were assessed several times between baseline and a 45-min post-stress recovery period. There were modest changes in adiposity measures while the adipokine leptin was markedly reduced (−27%) after the intervention. Blood pressure reactivity was attenuated (−3.38 ± 1.39 mmHg) and heart rate recovery was improved (2.07 ± 0.96 Bpm) after weight loss. Blood pressure responses were inversely associated with changes in waist to hip ratio post intervention. Decreased levels of circulating leptin following weight loss were inversely associated with the IL-6 inflammatory response to stress (r = −0.47). We offered preliminary evidence suggesting that modest changes in adiposity following a brief caloric restriction program may yield beneficial effect on cardiovascular stress responses. In addition, reductions in basal leptin activity might be important in blunting pro-inflammatory responses. Large randomized trials of the effect of adiposity on autonomic responses are thus warranted.

Learning aptitude, spatial orientation and cognitive flexibility tested in a virtual labyrinth after virtual stress induction.

BackgroundUnder stressful conditions such as in an emergency situation, efficient information processing is essential for reasonable responses.Purpose of the Study: Virtual Reality (VR) technology is used to induce stress and to test three main cognitive functions for decision making in stressful situations.MethodsA VR task was developed to induce stress following the Trier Social Stress Test (TSST) protocol and two VR cognitive performance tests to measure learning aptitude, spatial orientation and cognitive flexibility. Participants (N = 31) gave a public speech in front of a virtual audience (TSST) and later had to find their way out of different VR labyrinths. The first exercise tested spatial orientation and learning aptitude where participants had to learn aspects of the ground layout and geometric icons had to be identified as correct in order to be able to exit. The second labyrinth tested cognitive flexibility on the background of the Wisconsin Card Sorting Test.Statistical tests: Correlations were analyzed using Kendall Tau Correlation (One-tailed tests with p set to 0.05 for all analyses). Heart rate (HR) was calculated from the RR time values and averaged across the TSST- speech and the post-stress period. Autonomic nervous system reactivity was defined as the deviation of HR during TSST- speech condition from post-stress baseline measurement. A repeated-measures t-test was used to analyze differences.ResultsThe newly developed virtual stress test was successfully adapted from the original TSST. Participants perceived the task as stressful and scored an average of 5.7 points on a 1–8 Likert Scale. As a physiological stress parameter, increased heart rates of the participants showed that they were more stressed during the TSST procedure compared to the post-stress period. Also, the subjective stress perception, has a strong correlation with the results of the cognitive tasks performed after the stress induction.ConclusionsThe more a participant experienced the TSST as stressful, the lower their learning aptitude and spatial orientation were found to be at the end of the study. On the other hand, if someone perceived the virtual TSST as “unexpected”, as an indicator for a mild stress response, their cognitive flexibility was improved.Potential Implications: The findings indicate that both, the VR stress induction scenario using TSST, as well as the VR cognitive tests, are a first successful step towards a better ecological validity in neuropsychological testing.

Repeated psychosocial stress at night affects the circadian activity rhythm of male mice.

We have recently shown that molecular rhythms in the murine suprachiasmatic nucleus (SCN) are affected by repeated social defeat (SD) during the dark/active phase (social defeat dark [SDD]), while repeated SD during the light/inactive phase (social defeat light [SDL]) had no influence on PERIOD2::LUCIFERASE explant rhythms in the SCN. Here we assessed the effects of the same stress paradigm by in vivo biotelemetry on 2 output rhythms of the circadian clock (i.e., activity and core body temperature) in wild-type (WT) and clock-deficient Period (Per)1/2 double-mutant mice during and following repeated SDL and SDD. In general, stress had more pronounced effects on activity compared to body temperature rhythms. Throughout the SD procedure, activity and body temperature were markedly increased during the 2 h of stressor exposure at zeitgeber time (ZT) 1 to ZT3 (SDL mice) and ZT13 to ZT15 (SDD mice), which was compensated by decreased activity during the remaining dark phase (SDL and SDD mice) and light phase (SDL mice) in both genotypes. Considerable differences in the activity between SDL and SDD mice were seen in the poststress period. SDD mice exhibited a reduced first activity bout at ZT13, delayed activity onset, and, consequently, a more narrow activity bandwidth compared with single-housed control (SHC) and SDL mice. Given that this effect was absent in Per1/2 mutant SDD mice and persisted under constant darkness conditions in SDD WT mice, it suggests an involvement of the endogenous clock. Taken together, the present findings demonstrate that SDD has long-lasting consequences for the functional output of the biological clock that, at least in part, appear to depend on the clock genes Per1 and Per2.

Sex-specific impairment and recovery of spatial learning following the end of chronic unpredictable restraint stress: Potential relevance of limbic GAD

Chronic restraint stress alters hippocampal-dependent spatial learning and memory in a sex-dependent manner, impairing spatial performance in male rats and leaving intact or facilitating performance in female rats. Moreover, these stress-induced spatial memory deficits improve following post-stress recovery in males. The current study examined whether restraint administered in an unpredictable manner would eliminate these sex differences and impact a post-stress period on spatial ability and limbic glutamic acid decarboxylase (GAD65) expression. Male (n=30) and female (n=30) adult Sprague–Dawley rats were assigned to non-stressed control (Con), chronic stress (Str-Imm), or chronic stress given a post-stress recovery period (Str-Rec). Stressed rats were unpredictably restrained for 21 days using daily non-repeated combinations of physical context, duration, and time of day. Then, all rats were tested on the radial arm water maze (RAWM) for 2 days and given one retention trial on the third day, with brains removed 30min later to assess GAD65 mRNA. In Str-Imm males, deficits occurred on day 1 of RAWM acquisition, an impairment that was not evident in the Str-Rec group. In contrast, females did not show significant outcomes following chronic stress or post-stress recovery. In males, amygdalar GAD65 expression negatively correlated with RAWM performance on day 1. In females, hippocampal CA1 GAD65 positively correlated with RAWM performance on day 1. These results demonstrate that GABAergic function may contribute to the sex differences observed following chronic stress. Furthermore, unpredictable restraint and a recovery period failed to eliminate the sex differences on spatial learning and memory.

Conversation with Charles P. O'Brien

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