Repeated Stress Research Articles

The effects of cortisol on cytokine secretion and gene expression in human microglia models of single and repeated stress

The effects of cortisol on cytokine secretion and gene expression in human microglia models of single and repeated stress

Regulatory role of cytokines on etiology of depression in animal models: their biological mechanisms and clinical implication with physical exercise.

It has been known that chronic psychological or physical stress elicits depressive behaviors (learned helplessness, anhedonia, anxiety, etc.) and also activates to release proinflammatory cytokines in the brain. Especially, postmenopausal women under stress condition exacerbates neuroimmune systems and mood disorder. Repeated restraint stress in the ovariectomized female rats poses an immune challenge which was capable of inducing depressive-like behaviors, promoting exaggerated corticosterone responses and changing the proinflammatory cytokine expression such as interleukin (IL)-1β in the brain. Also, anti-inflammatory cytokines including IL-4 are known to regulate inflammation caused by immune response or stress challenge. Furthermore, some studies reported that physical activity can reduce stress hormones and improve personal immunity. Physical exercise has been shown to be associated with decreased symptoms of depression and anxiety, and with improved physical health, immunological function, and psychological well-being. This paper aims to discuss an overview of how stress shapes neuroimmune response and diverse roles of cytokines in animals models, acting on depressive-like behavioral changes; some beneficial aspects of exercise on stress-related disorders are addressed.

The Oil Formulation Derived from Moringa Oleifera Seeds Ameliorates Behavioral Abnormalities in Water-immersion Restraint Stress Mouse Model.

Repeated stress events are well known to be associated with the onset of behavioral abnormalities including depression, anxiety and memory impairment. In spite of the traditional uses of Moringa oleifera (MO), no experimental evidence for its use against chronic stress exists. Here, we investigated whether seed oil from MO (MOO) could improve behavior abnormalities of chronic stress mice induced by water-immersion restraint stress (WIRS) and the underlying mechanism. BALB/C male mice at 12 weeks of age were exposed to chronic WIRS for two weeks and divided in to four groups: normal group, WIRS group, WIRS+MOO1 group (treated with MOO at the dose of 1 mL/kg BW), and WIRS+MOO2 group (treated with MOO 2 mL/kg BW). The MOO treatment was given orally for 23 days. On day 24, we checked the behavior parameters, the plasma level of cortisol, acetylcholinesterase (AChE) activity in hippocampus, mRNA expression level of brain-derived neurotrophic factor (BDNF) and oxidative stress parameters in brain tissues. In addition, we also checked the histopathological features of the gastric mucosa wall. Administration of MOO ameliorated anxiety-like, depression-like and memory impairment phenotypes in the WIRS mouse model although the plasma cortisol concentrations were comparable among the groups. Of note, MOO both in two doses could suppress the AChE activity in hippocampus tissue and ameliorated the MDA level in prefrontal cortex tissue in mice exposed to WIRS. Although only WIRS+MOO2 group could increase the mRNA expression of BDNF, the histopathological gastric mucosa wall features were improved in all MOO groups. Taken together, these finding suggested that MOO may have a neuroprotective effect in the mouse model of WIRS as evidenced by improving the abnormal behaviors through enhancing mRNA expression level of BDNF, inhibited AChE activity, and prevented the increase of MDA level in the brain.

Kappa opioid receptor agonists produce sexually dimorphic and prolactin-dependent hyperalgesic priming.

Repeated stress produces hyperalgesic priming in preclinical models, but underlying mechanisms remain uncertain. As stress engages kappa opioid receptors (KORs), we hypothesized that repeated administration of KOR agonists might mimic, in part, stress-induced hyperalgesic priming. The potential contribution of circulating prolactin (PRL) and dysregulation of the expression of PRL receptor (PRLR) isoforms in sensory neurons after KOR agonist administration was also investigated. Mice received 3 daily doses of U-69593 or nalfurafine as a "first-hit" stimulus followed by assessment of periorbital tactile allodynia. Sixteen days after the first KOR agonist administration, animals received a subthreshold dose of inhalational umbellulone, a TRPA1 agonist, as the second-hit stimulus and periorbital allodynia was assessed. Cabergoline, a dopamine D2 receptor agonist, was used to inhibit circulating PRL in additional cohorts. Prolactin receptor isoforms were quantified in the V1 region of the trigeminal ganglion after repeated doses of U-69593. In both sexes, KOR agonists increased circulating PRL and produced allodynia that resolved within 14 days. Hyperalgesic priming, revealed by umbellulone-induced allodynia in animals previously treated with the KOR agonists, also occurred in both sexes. However, repeated U-69593 downregulated the PRLR long isoform in trigeminal neurons only in female mice. Umbellulone-induced allodynia was prevented by cabergoline co-treatment during priming with KOR agonists in female, but not male, mice. Hyperalgesic priming therefore occurs in both sexes after either biased or nonbiased KOR agonists. However, a PRL/PRLR-dependence is observed only in female nociceptors possibly contributing to pain in stress-related pain disorders in females.

Reliability assessment of parallel wire suspender components considering interlayer corrosion variance

The suspenders bear the repeated stress caused by various cyclic actions during the bridge operation while the stress amplitude under dynamic load is smaller than under dead load. The steel wire degradation process is a typical corrosion fatigue degradation, in which the initial defects caused by surface corrosion are the main source of fatigue cracks and the crack development under operating load leads to the failure of the steel wire. The steel wires of the suspender are considered as a co-deformed parallel structural system. The corrosion process of steel wires in different layers are different for the diffusion paths of corrosion medium, which makes the bearing capacity of steel wires differs from each other. The suspender strength depends on the wire of lowest strength due to the Daniels effect, interlayer corrosion variance should be considered in the evaluation of suspender reliability. This paper investigates the interlayer corrosion variance of parallel steel wire suspenders on the basis of neutral salt spray test. It proposes a corrosion variance coefficient, and considers the stochastic degradation process of suspender. Combined with the daily traffic model, it establishes a sophisticated reliability evaluation method of suspender. The results are shown: The steel wires in each layer of test specimens are all severely corroded when the corrosion time reaches a certain degree. For the specimens with different damage types, the overall corrosion condition of the annular damaged specimen is the most severe; whereas that of the vertical damaged specimen is the least. Under experimental environment, the corrosion variance coefficients of sheath damaged specimens follow normal distribution. In the application of suspender evaluation, the service lifespan of wires varies obviously with the corrosion variance coefficient. The distribution of steel wire lifespan under different corrosion variance coefficients also follows normal distribution. The service lifespan of outer layer wires is longer than inner layer wires, and the overall reliability lies between the reliability of outer and inner layers.

Restraint Stress and Repeated Corticosterone Administration Differentially Affect Neuronal Excitability, Synaptic Transmission and 5-HT7 Receptor Reactivity in the Dorsal Raphe Nucleus of Young Adult Male Rats.

Exogenous corticosterone administration reduces GABAergic transmission and impairs its 5-HT7 receptor-dependent modulation in the rat dorsal raphe nucleus (DRN), but it is largely unknown how neuronal functions of the DRN are affected by repeated physical and psychological stress. This study compared the effects of repeated restraint stress and corticosterone injections on DRN neuronal excitability, spontaneous synaptic transmission, and its 5-HT7 receptor-dependent modulation. Male Wistar rats received corticosterone injections for 7 or 14 days or were restrained for 10 min twice daily for 3 days. Repeated restraint stress and repeated corticosterone administration evoked similar changes in performance in the forced swim test. They increased the frequency of spontaneous excitatory postsynaptic currents (sEPSCs) recorded from DRN neurons. In contrast to the treatment with corticosterone, restraint stress-induced changes in sEPSC kinetics and decreased intrinsic excitability of DRN neurons did not modify inhibitory transmission. Repeated injections of the 5-HT7 receptor antagonist SB 269970 ameliorated the effects of restraint on excitability and sEPSC frequency but did not restore the altered kinetics of sEPSCs. Thus, repeated restraint stress and repeated corticosterone administration differ in consequences for the intrinsic excitability of DRN projection neurons and their excitatory and inhibitory synaptic inputs. Effects of repeated restraint stress on DRN neurons can be partially abrogated by blocking the 5-HT7 receptor.

Stress induced aging in mouse eye.

Aging, a universal process that affects all cells in an organism, is a major risk factor for a group of neuropathies called glaucoma, where elevated intraocular pressure is one of the known stresses affecting the tissue. Our understanding of molecular impact of aging on response to stress in retina is very limited; therefore, we developed a new mouse model to approach this question experimentally. Here we show that susceptibility to response to stress increases with age and is primed on chromatin level. We demonstrate that ocular hypertension activates a stress response that is similar to natural aging and involves activation of inflammation and senescence. We show that multiple instances of pressure elevation cause aging of young retina as measured on transcriptional and DNA methylation level and are accompanied by local histone modification changes. Our data show that repeated stress accelerates appearance of aging features in tissues and suggest chromatin modifications as the key molecular components of aging. Lastly, our work further emphasizes the importance of early diagnosis and prevention as well as age-specific management of age-related diseases, including glaucoma.

Habit Formation and the Effect of Repeated Stress Exposures on Cognitive Flexibility Learning in Horses.

Simple SummaryHorse training exposes horses to many difficult learning challenges, including tasks that run counter to their natural behaviour and research from neuroscience can be used to understand how horses respond to these learning challenges. Horses can also quickly develop habits, however if the habit is undesirable, the horse may be subjected to retraining where it must learn to suppress the unwanted behaviour and learn a new response. This is called cognitive flexibility and is underpinned by complex neural processes and can be impaired by exposure to repeated or chronic stress. We trained horses to acquire habit-like responses in one of two industry-style aversive instrumental learning scenarios (moving away from the stimulus-instinctual-IS or moving towards the stimulus-non-instinctual-NIS) and evaluated the effect of repeated stress exposures on their cognitive flexibility in a reversal task. We measured heart rate, salivary cortisol and serum brain derived neurotrophic factor to infer possible neural correlates of the learning outcomes. Horses trained in the NIS task took longer to learn task than the horses trained in the IS task, however they were quicker to learn the IS task during the reversal. There was no significant effect of the stress exposures on cognitive flexibility, however the stress did make horses more sensitive to the aversive training stimuli. These results provide guidance for trainers to adapt their practices when training tasks that are difficult for horses to learn and during retraining. In particular, even when horses have been trained to approach aversive stimuli they can quickly learn to avoid them. This has implications for retraining unwanted responses during aversive situations such as trailer loading.Horse training exposes horses to an array of cognitive and ethological challenges. Horses are routinely required to perform behaviours that are not aligned to aspects of their ethology, which may delay learning. While horses readily form habits during training, not all of these responses are considered desirable, resulting in the horse being subject to retraining. This is a form of cognitive flexibility and is critical to the extinction of habits and the learning of new responses. It is underpinned by complex neural processes which can be impaired by chronic or repeated stress. Domestic horses may be repeatedly exposed to multiples stressors. The potential contribution of stress impairments of cognitive flexibility to apparent training failures is not well understood, however research from neuroscience can be used to understand horses’ responses to training. We trained horses to acquire habit-like responses in one of two industry-style aversive instrumental learning scenarios (moving away from the stimulus-instinctual or moving towards the stimulus-non-instinctual) and evaluated the effect of repeated stress exposures on their cognitive flexibility in a reversal task. We measured heart rate as a proxy for noradrenaline release, salivary cortisol and serum Brain Derived Neurotrophic Factor (BDNF) to infer possible neural correlates of the learning outcomes. The instinctual task which aligned with innate equine escape responses to aversive stimuli was acquired significantly faster than the non-instinctual task during both learning phases, however contrary to expectations, the repeated stress exposure did not impair the reversal learning. We report a preliminary finding that serum BDNF and salivary cortisol concentrations in horses are positively correlated. The ethological salience of training tasks and cognitive flexibility learning can significantly affect learning in horses and trainers should adapt their practices where such tasks challenge innate equine behaviour.

Temporomandibular joint disorders: current concepts for conservative management

The temporomandibular joint is subject to repeated stress. The overloading of the compensation system leads to dysfunction, which manifests itself in the form of muscular and articular damage. Pain, joint noises and limitation of mouth opening are the most frequent reasons for a temporomandibular dysfunction (TMD) consultation. The diagnosis is mainly clinical. The therapeutic concepts are still controversial. The aim of this article is to offer a management strategy based on evidence through the analysis of literature reviews.

Sex differences in electrophysiological properties and voltage-gated ion channel expression in the paraventricular thalamic nucleus following repeated stress.

BackgroundHabituation to repeated stress refers to a progressive reduction in the stress response following multiple exposures to the same, predictable stressor. We previously demonstrated that the posterior division of the paraventricular thalamic nucleus (pPVT) nucleus regulates habituation to 5 days of repeated restraint stress in male rats. Compared to males, female rats display impaired habituation to 5 days of restraint. To better understand how activity of pPVT neurons is differentially impacted in stressed males and females, we examined the electrophysiological properties of pPVT neurons under baseline conditions or following restraint.MethodsAdult male and female rats were exposed to no stress (handling only), a single period of 30 min restraint or 5 daily exposures to 30 min restraint. 24 h later, pPVT tissue was prepared for recordings.ResultsWe report here that spontaneous excitatory post-synaptic current (sEPSC) amplitude was increased in males, but not females, following restraint. Furthermore, resting membrane potential of pPVT neurons was more depolarized in males. This may be partially due to reduced potassium leakage in restrained males as input resistance was increased in male, but not female, rats 24 h following 1 or 5 days of 30-min restraint. Reduced potassium efflux during action potential firing also occurred in males following a single restraint as action potential half-width was increased following a single restraint. Restraint had limited effects on electrophysiological properties in females, although the mRNA for 10 voltage-gated ion channel subunits was altered in the pPVT of female rats.ConclusionsThe results suggest that restraint-induced changes in pPVT activation promote habituation in males. These findings are the first to describe a sexual dimorphism in stress-induced electrophysiological properties and voltage-gated ion channel expression in the pPVT. These results may explain, at least in part, why habituation to 5 days of restraint is disrupted in female rats.

A Charcot-Marie-Tooth-Causing Mutation in HSPB1 Decreases Cell Adaptation to Repeated Stress by Disrupting Autophagic Clearance of Misfolded Proteins.

Charcot-Marie-Tooth (CMT) disease is the most common inherited neurodegenerative disorder with selective degeneration of peripheral nerves. Despite advances in identifying CMT-causing genes, the underlying molecular mechanism, particularly of selective degeneration of peripheral neurons remains to be elucidated. Since peripheral neurons are sensitive to multiple stresses, we hypothesized that daily repeated stress might be an essential contributor to the selective degeneration of peripheral neurons induced by CMT-causing mutations. Here, we mainly focused on the biological effects of the dominant missense mutation (S135F) in the 27-kDa small heat-shock protein HSPB1 under repeated heat shock. HSPB1S135F presented hyperactive binding to both α-tubulin and acetylated α-tubulin during repeated heat shock when compared with the wild type. The aberrant interactions with tubulin prevented microtubule-based transport of heat shock-induced misfolded proteins for the formation of perinuclear aggresomes. Furthermore, the transport of autophagosomes along microtubules was also blocked. These results indicate that the autophagy pathway was disrupted, leading to an accumulation of ubiquitinated protein aggregates and a significant decrease in cell adaptation to repeated stress. Our findings provide novel insights into the molecular mechanisms of HSPB1S135F-induced selective degeneration of peripheral neurons and perspectives for targeting autophagy as a promising therapeutic strategy for CMT neuropathy.

Repeated stress exposure leads to structural synaptic instability prior to disorganization of hippocampal coding and impairments in learning

Stress exposure impairs brain structure and function, resulting in cognitive deficits and increased risk for psychiatric disorders such as depression, schizophrenia, anxiety and post-traumatic stress disorder. In particular, stress exposure affects function and structure of hippocampal CA1 leading to impairments in episodic memory. Here, we applied longitudinal deep-brain optical imaging to investigate the link between changes in activity patterns and structural plasticity of dorsal CA1 pyramidal neurons and hippocampal-dependent learning and memory in mice exposed to stress. We found that several days of repeated stress led to a substantial increase in neuronal activity followed by disruption of the temporal structure of this activity and spatial coding. We then tracked dynamics of structural excitatory connectivity as a potential underlying cause of the changes in activity induced by repeated stress. We thus discovered that exposure to repeated stress leads to an immediate decrease in spinogenesis followed by decrease in spine stability. By comparison, acute stress led to stabilization of the spines born in temporal proximity to the stressful event. Importantly, the temporal relationship between changes in activity levels, structural connectivity and activity patterns, suggests that loss of structural connectivity mediates the transition between increased activity and impairment of temporal organization and spatial information content in dorsal CA1 upon repeated stress exposure.

Effects of chronic stress on nectin1 levels in the mouse primary somatosensory cortex

Chronic exposure to stressful experiences impairs synaptic plasticity. Previous studies have shown that the spine densities of pyramidal neurons, the turnover of mushroom-type spines, and the excitatory–inhibitory balance in the primary somatosensory cortex (S1) are modulated by stress. Trans-synaptic cell adhesion molecules (CAMs) are implicated in stress-induced synaptic deficits. However, it remains unknown whether stress dysregulates CAMs in S1 and thereby impairs synaptic plasticity. In this study, we applied the early-life stress (ELS), chronic social defeat stress (CSDS), and chronic restraint stress paradigms and measured the mRNA levels of <i>nectin1</i> in S1 of wild-type and conditional forebrain corticotropin-releasing hormone receptor 1 type (CRHR1) conditional knockout mice. We found that ELS increased <i>nectin1</i> mRNA levels in S1 in adult but not adolescent mice. Moreover, CSDS increased the <i>nectin1</i> mRNA levels in S1 in adult mice via the CRH-CRHR1 system. Our findings suggest that S1 is vulnerable to repeated stress exposures at some life stages, and dysregulated <i>nectin1</i> expression may underlie stress-induced structural and functional abnormalities in S1.

The Pituitary-Adrenal Response to Paradoxical Sleep Deprivation Is Similar to a Psychological Stressor, Whereas the Hypothalamic Response Is Unique.

Stressors of different natures induce activation of the hypothalamic-pituitary-adrenal (HPA) axis at different magnitudes. Moreover, the HPA axis response to repeated exposure is usually distinct from that elicited by a single session. Paradoxical sleep deprivation (PSD) augments ACTH and corticosterone (CORT) levels, but the nature of this stimulus is not yet defined. The purpose of the present study was to qualitatively compare the stress response of animals submitted to PSD to that of rats exposed once or four times to cold, as a physiological stress, movement restraint (RST) as a mixed stressor and predator odour (PRED) as the psychological stressor, whilst animals were submitted for 1 or 4 days to PSD and respective control groups. None of the stressors altered corticotropin releasing factor immunoreactivity in the paraventricular nucleus of the hypothalamus (PVN), median eminence (ME) or central amygdala, compared to control groups, whereas vasopressin immunoreactivity in PSD animals was decreased in the PVN and increased in the ME, indicating augmented activity of this system. ACTH levels were higher after repeated stress or prolonged PSD than after single- or 1 day-exposure and control groups, whereas the CORT response was habituated by repeated stress, but not by 4-days PSD. This dissociation resulted in changes in the CORT : ACTH ratio, with repeated cold and RST decreasing the ratio compared to single exposure, but no change was seen in PRED and PSD groups. Comparing the magnitude and pattern of pituitary-adrenal response to the different stressors, PSD-induced responses were closer to that shown by PRED-exposed rats. In contrast, the hypothalamic response of PSD-exposed rats was unique, inasmuch as this was the only stressor which increased the activity of the vasopressin system. In conclusion, we propose that the pituitary-adrenal response to PSD is similar to that induced by a psychological stressor.

Stress and adaptation to repeated stress changed the expression of two isoforms of 11β-hydroxysteroid dehydrogenase (11β-HSD1 and 11β-HSD2) in the adrenal glands of sheep

The aim of this study was to estimate rate of cortisol release from ewe’s adrenal gland cortex and medulla tissue and the participation 11β-HSD1 and 2 in modulating adrenal glucocorticosteroids release, determine the expression size of these two isoforms in both parts of adrenal glands after single and repeated stress (3 times every 24h), when adaptive processes take place. The experiment was carried on 15 ewes, outside the breeding season. The research material consisted of adrenal glands obtained from control sheep (CON), sheep subjected to one-hour individual isolation from the herd (S1) and three times repeated stress factor at one-day intervals (S2). Immediately after slaughter, the adrenal glands from each sheep were placed on ice in 0.9% NaCl, then they were cut into smaller sections of similar weight (approx. 50 mg), covering the cortical and medullary layers of the adrenal glands. Sections of obtained tissues were weighed and placed in incubation wells (Sigma cell culture) containing 1 ml of incubation Eagle's medium with the addition of bovine albumin (BSA, 50 mg / 100 ml). Tissue incubation was carried out in an atmosphere of carbogen - 95% O2 and 5% CO2 at 38oC in a Sanyo incubator (MCO-18AIC). After 10 minutes of stabilization, the sections of core and adrenal cortex tissue were transferred to subsequent wells containing pure Eagle Medium. The same section was transferred to consecutive incubation wells containing clean incubation medium every 30 minutes. The medium harvested from the wells after 30, 60 and 90 minutes of incubation of adrenal tissue was frozen until the scheduled cortisol concentration de-termination by RIA (Orion Diagnostica) was performed. Another pieces of tissue the cortex and adrenal medulla from each sheep immediately placed in the RNAlater. Measurements of the gene expression of 11β-HSD1 and 2 expression in the adrenal cortex and medulla were performed using Real-time qPCR method. Starters and TaqMan MGB probes were designed by Applied Biosystem. In the conducted in vitro experiment, a significant reduction in the amount of cortisol released from adrenal cortex tissue into the medium after single stress factor was found, from 3.27 ± 0.69 pg･mg-1 tissue after first 30 minutes of experiment to 0.70 ± 0.15 pg･mg-1 of tissue after 90 minutes (P &lt; 0.01). A similar profile of cortisol release from the adrenal cortex tissue was found in control sheep (P &gt; 0.05). Experimental Group 2 (S2) had a similar profile of cortisol release during the all-time of incubation, however the values found were always lower than those observed in the control and single stress sheep Experimental Group 1 (S1) (1.34 ± 0.37 to 0.30 ± 0.08 pg･mg-1 of tissue; P &lt; 0.05). After repeated stress, incubation of adrenal cortex tissue showed a similar profile of changes in cortisol release, however the values were significantly lower than those found in the singly stressed animals (from 1.30 ± 0.37 pg･mg-1 after 30 minutes to 0.27 ± 0.08 pg･mg-1 tissue after 90 minutes; P &lt; 0.01). Incubation of adrenal medulla tissue obtained from singly stressed animals showed cortisol release to the medium much lower in comparison to adrenal cortex layer, however constant during the whole incubation time, value 1.04 ± 0.36 pg/mg-1 tissue noted after first 30 minutes to 0.77 ± 0.06 pg･mg-1 after 90 minutes of experiment; P &gt; 0.05). When the stress factor was repeated three times, the amount of cortisol released was like that observed in the control secretion; P &gt; 0.05). Analysis of 11β-HSD 1 expression in adrenal cortex tissue from singly stressed sheep showed an over threefold increase (350 ± 25 RQ), while measurement after stress factor was repeated three times demonstrated increase, however the value turned out to be two times lower than after a single stress (160 ± 35 RQ). The expression value of 11β-HSD 2 in the adrenal cortex tissue showed a significant reduction after both single (15 ± 7 RQ and repeated stress (22 ± 3.0 RQ). No significant differences were found in the expression value of this enzyme in the sheep adrenal medulla in both experimental groups in comparison to control group (P &gt; 0.05). The obtained results indicate the immanent abilities of the adrenal glands, probably to a certain extent, to control the release of cortisol, conditioned by the presence and variable activity of the enzyme 11β-HSD, particularly isoform 1, in adrenal glands without the need to activate all HPA axis structures during stress and adaptation processes.

Preliminary longitudinal evidence for stability of maternal behavior and infant stress regulation among infants born preterm at 4 and 9 months during the Still Face paradigm

Stress regulation begins to develop in the first year of life through interactions with caregivers, particularly in the presence of stressors. High quality caregiving, characterized by maternal sensitivity and responsiveness to the infant’s emotional cues, is particularly important in the development of infant stress regulation. The purpose of this study was to assess the longitudinal stability of, and associations between, maternal interactive behavior and infant stress regulation (indexed by positive infant affect and cortisol reactivity) in response to the Still Face paradigm (SF) in a cohort of infants born preterm (< 32 weeks gestation, N = 22) at four months and nine months (adjusted age). The percent of time mothers spent using specific interaction styles (contingent maternal interaction (CMI), attention seeking, and watching) during Play/baseline, Reunion#1, and Reunion#2 SF episodes was calculated To assess infant stress regulation, two indices were obtained at both 4 and 9 months during the SF paradigm: the percent of positive affect displayed over each SF episode (0-100%) and a neuroendocrine stress response score based on salivary cortisol reactivity. We found three non-significant but medium-large effect size differences between 4 and 9 month variables, with more positive findings at 9 months. Regarding stability within the 4 month and 9 month episodes, maternal behavior and positive infant affect were non-significantly but moderately stable, with maternal watching behavior being particularly stable. Positive infant affect stability between Reunion#1 and Reunion#2 at 4 months was significantly greater than positive infant affect stability across these two episodes at 9 months. Regarding stability across 4 and 9 month (same) episodes, CMI and positive infant affect showed modest but non-significant stability across (same) 4 and 9 month episodes. Finally, with positive infant affect at Reunion#2 as the “outcome” of the Still Face, CMI at both 4 month Play and Reunion#1 episodes were significantly correlated with this “outcome.” Further, positive infant affect at Reunion#2 was more strongly correlated with CMI at both Play and Reunion#1 for 4 month old compared with 9 month old infants. Thus, sensitive care appears particularly important for younger infants born preterm, and mothers’ behavior early in a repeated stress exposure paradigm may be particularly important in maintaining positive infant affect and in the development of infants’ stress regulation more generally. Identifying the longer-term effects of early stress on infant stress regulation, and its relationship with maternal interaction, has important implications for understanding trajectories of regulatory patterns and deficits. A greater understanding of these relationships is particularly important given that greater emotion and neuroendocrine stress regulation in infancy have been directly associated with numerous positive outcomes throughout childhood.

How distinct killifish populations respond differently to stress

Down the east coast of North America, populations of Atlantic killifish, Fundulus heteroclitus, experience wildly different thermal environments. Southern populations experience water that is, on average, 12°C hotter than northern populations annually. These northern and southern killifish populations cope with stress differently. When fish are stressed, such as when predators are nearby, they activate a suite of mechanisms that regulate the release of the stress hormone cortisol, allowing the fish to remain in good condition. Researchers found previously that killifish from southern populations had higher plasma cortisol levels than killifish from northern populations after they experienced the same stress. To figure out why some fish respond strongly to stress while others do not, Madison Earhart and co-workers from the University of British Columbia, Canada, with colleagues from the University of Manitoba, Canada, and the University of Glasgow, UK, set out to determine what genes are responsible for the differences in killifish stress responses by investigating different mechanisms that trigger cortisol release after experiencing stress.Earhart and colleagues travelled to the USA and collected adult killifish from northern New Hampshire and southern Georgia populations. Then, they brought the fish back to the lab in British Columbia. First, the team wanted to see whether the differences in population stress response changed when the fish experienced stress briefly or were exposed to the same stress repeatedly over the period of a week by either putting the fish in buckets and shaking them for half an hour or repeatedly shaking them every day for a week. After stressing the fish, the team collected samples of the fish's blood to measure their cortisol plasma levels, in addition to collecting samples of the fish's brain, head kidney – the organ that produces cortisol – and liver – the organ that produces and breaks down glucose – to measure the expression of genes important for the production and release of cortisol due to stress.After experiencing the single stressful situation, the southern killifish population had higher cortisol levels than the northern killifish population. However, when the fish were repeatedly stressed over the period of a week, there was no difference in cortisol levels between the northern and southern populations. The southern population of killifish, which had a stronger response to the individual stressful situation, expressed more of the genes involved in cortisol production in the brain and head kidney. In addition, the livers of fish from the southern population were more responsive to the cortisol stress hormone as they expressed larger amounts of the gene for the protein that triggers the protective mechanisms that are activated by cortisol when a fish is stressed.The team also measured the condition of the fish after repeated stress. They found that the southern killifish, which were more stress responsive than the northern killifish, were in better condition after experiencing repeated stress than were northern populations. This showed that responding to stress by increasing cortisol was beneficial for the southern population of fish.Earhart and colleagues noted that the answer as to why some fish respond more strongly to stress than others is more complex than simply increasing cortisol levels in the body. They showed that there are differences in the expression of genes all along the pathways that make cortisol, respond to cortisol and cease cortisol production in these two different populations of fish. Therefore, it is important to continue to study these differences in populations of the same species adapted to different environments.

Accelerated Cardiac Aging in Patients With Congenital Heart Disease.

An increasing number of patients with congenital heart disease (CHD) survive into adulthood but develop long-term complications including heart failure (HF). Cellular senescence, classically defined as stable cell cycle arrest, is implicated in biological processes such as embryogenesis, wound healing, and aging. Senescent cells have a complex senescence-associated secretory phenotype (SASP), involving a range of pro-inflammatory factors with important paracrine and autocrine effects on cell and tissue biology. While senescence has been mainly considered as a cause of diseases in the adulthood, it may be also implicated in some of the poor outcomes seen in patients with complex CHD. We propose that patients with CHD suffer from multiple repeated stress from an early stage of the life, which wear out homeostatic mechanisms and cause premature cardiac aging, with this term referring to the time-related irreversible deterioration of the organ physiological functions and integrity. In this review article, we gathered evidence from the literature indicating that growing up with CHD leads to abnormal inflammatory response, loss of proteostasis, and precocious age in cardiac cells. Novel research on this topic may inspire new therapies preventing HF in adult CHD patients.

Stress Elicits Contrasting Effects on Rac1-Cofilin Signaling in the Hippocampus and Amygdala.

There is accumulating evidence for contrasting patterns of stress-induced morphological and physiological plasticity in glutamatergic synapses of the hippocampus and amygdala. The same chronic stress that leads to the formation of dendritic spines in the basolateral amygdala (BLA) of rats, leads to a loss of spines in the hippocampus. However, the molecular underpinnings of these divergent effects of stress on dendritic spines are not well understood. Since the activity of the Rho GTPase Rac1 and the actin-depolymerizing factor cofilin are known to play a pivotal role in spine morphogenesis, we investigated if alterations in this signaling pathway reflect the differential effects of stress on spine plasticity in the hippocampus and amygdala. A day after the end of chronic immobilization stress (2 h/day for 10 days), we found a reduction in the activity of Rac1, as well as its effector p21-activated kinase 1 (PAK1), in the rat hippocampus. These changes, in turn, decreased cofilin phosphorylation alongside a reduction in the levels of profilin isoforms. In striking contrast, the same chronic stress increased Rac1, PAK1 activity, cofilin phosphorylation, and profilin levels in the BLA, which is consistent with enhanced actin polymerization leading to spinogenesis in the BLA. In the hippocampus, on the other hand, the same stress caused the opposite changes, the functional consequences of which would be actin depolymerization leading to the elimination of spines. Together, these findings reveal a role for brain-region specific differences in the dysregulation of Rac1-to-cofilin signaling in the effects of repeated stress on two brain areas that are implicated in the emotional and cognitive symptoms of stress-related psychiatric disorders.

Nano-priming: Impression on the beginner of plant life

In the interest to assist plant growth and bolster their strength to deal with the environmental cues, priming has been revealed to play a remarkable role through induction of several metabolic and physiological alterations. It can be delineated as a physiological process of prompting plants by treating with biological/chemical priming agents or mild stress to display better growth biomarkers and stress resistance in case of repeated stress encounters. Priming of seeds has been of great interest for researchers in recent years which brings about changes in seed metabolism to support the successful establishment of plants in its environment through faster and more prominent seed germination and growth of developing seedlings. The conspicuously displayed rise in applications of nanotechnology in agriculture has also stirred up the research on nano-priming of plants. Nanoparticles (NPs) have appeared to be more proficient in influencing growth, quality, yield, and reactive oxygen species (ROS) homeostasis in plant seeds than other methods of priming such as priming with the bulk materials or hydro-priming. However, there is a need to opt-out NPs exhibiting toxic effects on seed germination and seedling growth for deliberate priming while understanding their possible repercussions on plant as well as human health. Therefore, this article aims to present the recent research conducted in the field of nano-priming of seeds of different plants along with recommendations for future research.