Behavioral Responses To Stress Research Articles

Work-family conflict and salespeople deviant behavior: the mediating role of job stress

The salesperson is a job that is prone to deviant behavior. Prior studies addressed that deviant behavior is a behavioral stress response. Although numerous studies have demonstrated the relationship between job stress and deviant behavior, the clarity of the job stress mechanism remains limited. Drawing from coping theory, we proposed that job stress acts as a critical mechanism in linking the association between work-family conflict and salesperson deviant behavior. The objectives of this study are threefold. First, this study investigates the relationship between work-family conflict and job stress. Second, this study examines how job stress determines the likelihood of a salesperson engaging in deviant behavior. Last, this study investigates the mediating mechanism of work-family conflict and job stress. Using an online survey of salespeople in Indonesia, we received 321 data and employed a partial least square to test our proposed hypotheses. The results of this study confirm all hypotheses. The implications for managers regarding the result of this study is encouraging managers to establish and implement family-friendly policies which can diminish the level of stress and will decrease the likelihood of salespeople engaging in deviant behavior. Our study offers a significant contribution to the body of knowledge by clarifying the mediating role of job stress.

PSI-15 Effects of Melatonin on Behavioral and Physiological Responses of Weaned Beef Calves

Abstract Weaning is a stressful event often associated with changes in physiological characteristics, increased restlessness, reduced feed intake, and poor performance. This study was designed to evaluate the effects of melatonin on behavioral and physiological responses of weaned beef calves. Angus beef calves (n=36) at 7-mo of age were stratified by dam parity, body weight, calf sex and randomly allocated to receive either 24mg melatonin implants (MEL) or physiological saline (CON). A subset of calves were fitted with accelerometers on the hind leg to monitor activity levels for 7 days after weaning. Blood samples, rectal temperature, chute score and body weight measurements were collected on d 0, 7 and 14 after weaning. Activity of MEL calves was significantly (P < 0.05) lower than CON. The MEL calves had lower (P < 0.05) chute score on d 7 and 14 compared to CON. There was no marked effect of melatonin on rectal temperature and hematological parameters, however, platelet showed significant (P < 0.05) difference with MEL recording higher values compared to CON. Average daily gain (ADG) was 1.67 and 2.35kg/d in CON and MEL, respectively. We concluded that although no differences in ADG, hemogram, and rectal temperature were observed, melatonin treated calves had reduced behavioral stress response associated with weaning.

Effects of a Novel Gel Formulation of Dog Appeasing Pheromone (DAP) on Behavioral and Physiological Stress Responses in Dogs Undergoing Clinical Examination.

Simple SummarySafeguarding the health of dogs presupposes undergoing regular veterinary visits (VVs). However, the VV can be emotionally challenging, thus impairing the welfare of the patient, also reducing dog and owner compliance. The fear and anxiety experienced by the dogs evokes behavioral and physiological stress responses for adaptive purposes. It is therefore desirable to lower the stress from the visit. With this intent, we tested a gel formulation of a synthetic analogue of the appeasing pheromone secreted by bitches, the dog appeasing pheromone (DAP), as a situational support to improve the perception of the stay in the waiting room and the physical examination. In the waiting room, the dogs exposed to DAP exhibited changes in their behavior, namely significant decrease in lip licking, increase in panting, and nearly significant reduction of low body postures. On the examination table, neither behavioral nor physiological differences were found. DAP did not alter markedly the stress behavior and physiology of dogs during a VV, maybe due to a stress level exceeding the potential efficacy of the product. However, the change of a few stress-associated behaviors suggests that DAP could contribute to improving the welfare of dogs staying in the waiting room before the physical examination.The veterinary visit is necessary for safeguarding the health of dogs, but it can be stressful and threaten both the welfare of the patient and the accuracy of the examination. This randomized, triple-blind, placebo-controlled, crossover study aims at evaluating how dog appeasing pheromone (DAP) in a novel gel formulation influences the behavioral and physiological stress responses of 28 dogs undergoing a standardized clinical examination, while staying in the waiting room (WR) and visited in the examination room (ER). Behavioral responses were studied through behavioral categories and subjective scales (WR and ER). Autonomic response considered heart rate (WR and ER), blood pressure (WR and ER), respiratory rate (ER), and rectal temperature (ER). Neuroendocrine response considered salivary cortisol (WR and ER). In the waiting room, the use of DAP was associated with a significant reduction of lip licking (p = 0.0189), an increase in panting (p = 0.0276), and a reduction close to significance (p = 0.0584) of low body postures. No significant differences were observed within the physiological responses. In the examination room, neither behavioral nor physiological differences were found.

Sustained TNF signaling is required for the synaptic and anxiety-like behavioral response to acute stress

Acute stress triggers plasticity of forebrain synapses as well as behavioral changes. Here we reveal that Tumor Necrosis Factor α (TNF) is a required downstream mediator of the stress response in mice, necessary for stress-induced synaptic potentiation in the ventral hippocampus and for an increase in anxiety-like behaviour. Acute stress is sufficient to activate microglia, triggering the long-term release of TNF. Critically, on-going TNF signaling specifically in the ventral hippocampus is necessary to sustain both the stress-induced synaptic and behavioral changes, as these could be reversed hours after induction by antagonizing TNF signaling. This demonstrates that TNF maintains the synaptic and behavioral stress response in vivo, making TNF a potential novel therapeutic target for stress disorders.

Fatigue behavior and deformation mechanism of an as-cast Mg-Nd-Zr alloy tested at 150 °C

Increasing testing temperature significantly decreases the tensile and fatigue strengths of the as-cast Mg-3.73Nd-0.56Zr alloy. The stress amplitude of the as-cast alloy tested at 150 °C remains basically unchanged until fatigue failure. The deformation behavior of the as-cast alloy at elevated temperature mainly depends on <a> and <c> or <c + a> dislocation-slip and twinning. The cracks of the as-cast alloy mainly originate from casting defects. The competition between micro-hardening and micro-softening determines the stress response behavior of the as-cast alloy during cyclic loading. The formation of dislocation walls and the interaction of the dislocations with the eutectic phase particles and twin boundaries result in work hardening. In contrast, the micro-softening is attributed to the shearing of the dislocations on the twins and the formation of the micro-cracks on the surface of the fatigued samples.

Identification of activity-induced Egr3-dependent genes reveals genes associated with DNA damage response and schizophrenia

Bioinformatics and network studies have identified the immediate early gene transcription factor early growth response 3 (EGR3) as a master regulator of genes differentially expressed in the brains of patients with neuropsychiatric illnesses ranging from schizophrenia and bipolar disorder to Alzheimer’s disease. However, few studies have identified and validated Egr3-dependent genes in the mammalian brain. We have previously shown that Egr3 is required for stress-responsive behavior, memory, and hippocampal long-term depression in mice. To identify Egr3-dependent genes that may regulate these processes, we conducted an expression microarray on hippocampi from wildtype (WT) and Egr3−/− mice following electroconvulsive seizure (ECS), a stimulus that induces maximal expression of immediate early genes including Egr3. We identified 69 genes that were differentially expressed between WT and Egr3−/− mice one hour following ECS. Bioinformatic analyses showed that many of these are altered in, or associated with, schizophrenia, including Mef2c and Calb2. Enrichr pathway analysis revealed the GADD45 (growth arrest and DNA-damage-inducible) family (Gadd45b, Gadd45g) as a leading group of differentially expressed genes. Together with differentially expressed genes in the AP-1 transcription factor family genes (Fos, Fosb), and the centromere organization protein Cenpa, these results revealed that Egr3 is required for activity-dependent expression of genes involved in the DNA damage response. Our findings show that EGR3 is critical for the expression of genes that are mis-expressed in schizophrenia and reveal a novel requirement for EGR3 in the expression of genes involved in activity-induced DNA damage response.

Revealing the Increased Stress Response Behavior through Transcriptomic Analysis of Adult Zebrafish Brain after Chronic Low to Moderate Dose Rates of Ionizing Radiation

Simple SummaryThe increasing use of radiopharmaceuticals for medical diagnostics and radiotherapy raises concerns regarding health risks for both humans and the environment. Additionally, in the context of major nuclear accidents like in Chernobyl and Fukushima, very little is known about the effects of chronic exposure to low and moderate dose rates of ionizing radiation (IR). Many studies demonstrated the sensibility of the developmental brain, but little data exists for IR at low dose rates and their impact on adults. In this study, we characterized the molecular mechanisms that orchestrate stress behavior caused by chronic exposure to low to moderate dose rates of IR using the adult zebrafish model. We observed the establishment of a congruent stress response at both the molecular and individual levels.High levels of ionizing radiation (IR) are known to induce neurogenesis defects with harmful consequences on brain morphogenesis and cognitive functions, but the effects of chronic low to moderate dose rates of IR remain largely unknown. In this study, we aim at defining the main molecular pathways impacted by IR and how these effects can translate to higher organizational levels such as behavior. Adult zebrafish were exposed to gamma radiation for 36 days at 0.05 mGy/h, 0.5 mGy/h and 5 mGy/h. RNA sequencing was performed on the telencephalon and completed by RNA in situ hybridization that confirmed the upregulation of oxytocin and cone rod homeobox in the parvocellular preoptic nucleus. A dose rate-dependent increase in differentially expressed genes (DEG) was observed with 27 DEG at 0.05 mGy/h, 200 DEG at 0.5 mGy/h and 530 DEG at 5 mGy/h. Genes involved in neurotransmission, neurohormones and hypothalamic-pituitary-interrenal axis functions were specifically affected, strongly suggesting their involvement in the stress response behavior observed after exposure to dose rates superior or equal to 0.5 mGy/h. At the individual scale, hypolocomotion, increased freezing and social stress were detected. Together, these data highlight the intricate interaction between neurohormones (and particularly oxytocin), neurotransmission and neurogenesis in response to chronic exposure to IR and the establishment of anxiety-like behavior.

Chronic alcohol consumption alters home-cage behaviors and responses to ethologically relevant predator tasks in mice.

Alcohol withdrawal is a key component of severe alcohol use disorder. Animal models of alcohol withdrawal tend to focus on traditional anxiety/stress tests. While these have been essential to advancing our understanding of the biology of alcohol withdrawal, abrupt cessation of drinking following heavy alcohol consumption can also trigger withdrawal-related affective states that impact responses to a variety of life events and stressors. To this end, we show that behaviors in a variety of tasks that differ in task demand and intensity are altered during withdrawal in male and female mice after voluntary alcohol access. Male and female miceunderwent six weeks of intermittent two-bottle choice alcohol exposure followed by behavioral tests. The tests included-Home cage: low-stress baseline environment to measure spontaneous natural behaviors; Open field: anxiety-inducing bright novel environment; Looming disc: arena with a protective hut where mice are exposed to a series of discs that mimic an overhead advancing predator, and Robogator-simulated predator task: forced foraging behavioral choice in the presence of an advancing robot predator that "attacks" when mice are near a food pellet in a large open arena. A history ofalcohol exposure impacted behaviors in these tasks in a sex-dependent manner. In the home cage, alcohol induced reductions in digging and heightened stress coping through an increase in grooming time. In males, increased rearing yielded greater vigilance/exploration in a familiar environment. The open-field test revealed an anxiety phenotype in both male and female mice exposed to alcohol. Male mice showed no behavioral alterations to the looming disc task, while females exposed to alcohol showed greater escape responses than water controls, indicative of active stress-response behaviors. In males, the Robogator task revealed a hesitant/avoidant phenotype in alcohol-exposed mice under greater task demands. Few drugs show robust evidence of efficacy in clinical trials for alcohol withdrawal. Understanding how withdrawal alters a variety of behaviors in both males and females that are linked to stress coping can increase our understanding of alcohol misuse and aid in developing better medications for treating individuals with AUD.

Pre-probiotic effects of different bacterial species in aquaculture: behavioral, hematological and oxidative stress responses

There is very limited aquaculture research on candidate probiotics and their effects on fish physiology. In this study, acute applications of four different molecularly identified bacterial species – Brevibacillus brevis FD-1 (A), Pseudomonas fluorescens FDG-37 (B), Bacillus sphaericus FD-48 (C), and B. amyloliquefaciens TV-17C (D), with potential in aquaculture, were tested in rainbow trout (Oncorhynchus mykiss) under static conditions. Physiological changes in blood tissue [hematological indices: erythrocyte count (RBC), leukocyte count (WBC), hemoglobin (Hb), hematocrit (Hct), platelet count (PLT), mean cell hemoglobin concentration (MCHC), mean cell hemoglobin (MCH), and mean cell volume (MCV)], oxidative stress responses in liver and gill tissues [malondialdehyde (MDA) level, antioxidant enzyme activities: superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPX), glutathione reductase (GR), glutathione-S-transferase (GST), glucose-6-phosphate dehydrogenase (G6PD)] and acetylcholinesterase (AChE) activity in brain tissue (as neurotoxic biomarker) were investigated. Additionally, behavioral differences were recorded by measuring swimming performance to support neurotoxic findings in all treatment groups. The LC5024 value of FDG-37 strain was determined through analysis as 1.0 × 108 CFU ml-1. Inhibition of enzyme activity, increase in the MDA level, as well as significant differences in hematological indices and swimming performance were determined in rainbow trout treated with B compared to control and other bacterial groups in gills. The potential for using group FD-48 and TV-17C bacterial strains as probiotics in aquaculture is more pertinent when considering the research findings and water quality parameters.

Brief exposures to conspecific-derived alarm substance are sufficient to induce paternal intergenerational effects in zebrafish

Paternal intergenerational effects, whereby the father’s environment influences the phenotype of the offspring via molecular (e.g. epigenetic) changes to the sperm, comprise an area of active research in multiple biological contexts. Spermatogenesis is a critical window of sensitivity to environmental changes, such that males at full sexual maturity can acquire, incorporate, and transmit environmental information in spermatozoa. The degree of sensitivity is less clear, and as such previous experimental studies have typically relied on prolonged exposure regimes encapsulating the entire period of spermatogenesis. Here we exposed adult male zebrafish to a model stressor (conspecific-derived alarm substance, AS) in two 20-min episodes timed either shortly before or during the onset of spermatogenesis. There was no clear effect of paternal stress on a behavioural stress response in larval offspring but clear reductions in anxiety-like behaviour in juvenile offspring. Our findings suggest that prolonged exposures may not be required for the induction of measurable intergenerational responses in this popular vertebrate model.

Involvement of PKMζ in Stress Response and Depression.

The stress system in the brain plays a pivotal role in keeping humans and animals from harmful stimuli. However, excessive stress will cause maladaptive changes to the stress system and lead to depression. Despite the high prevalence of depression, the treatment remains limited. PKMζ, an atypical PKC isoform, has been demonstrated to play a crucial role in maintaining long-term potentiation and memory. Recent evidence shows that PKMζ is also involved in stress response and depressive-like behavior. In particular, it was demonstrated that stress that resulted in depressive-like behavior could decrease the expression of PKMζ in the prefrontal cortex, which could be reversed by antidepressants. Importantly, modulation of PKMζ expression could regulate depressive-like behaviors and the actions of antidepressants. These data suggested that PKMζ could be a molecular target for developing novel antidepressants. Here, I review the advance on the role of PKMζ in mediating stress response and its involvement in the development of depression.

Individual differences in spatial learning are correlated across tasks but not with stress response behaviour in guppies

Cognition is vital for carrying out behaviours required for survival and reproduction. Cognitive performance varies between species, but also between individuals within populations. While variation is a prerequisite for natural selection, selection does not act on traits in isolation. The extent to which cognitive traits covary with other aspects of phenotype (e.g. personality traits) may be important in shaping evolutionary dynamics. Here we adopted a multivariate approach to test spatial learning in male Poecilia reticulata and asked whether differences in cognitive performance are associated with (repeatable) differences in stress response behaviour. Functional links between cognitive traits and ‘stress coping style’ have been hypothesized. Furthermore, individual level studies of cognitive performance typically rely on multiple testing paradigms that may themselves be a stressor. There is a risk that variation in stress responsiveness is itself a cause of apparent, but artefactual variance in cognitive ability. Fish repeatedly experienced two spatial learning tasks (maze layouts) and an acute stress response test (open field trial). We found repeatable differences between individuals in performance within and across maze layouts. On average, performance improved with experience in the first maze, consistent with spatial learning, but not in the second. Individuals varied in the trajectory of mean performance with trial number in both mazes, suggesting they differ in ‘learning rate’. Acute stress response behaviour was repeatable but predicted neither average time to solve the maze nor learning rate. We found no support for between-individual correlation between acute stress response and cognitive performance. However, we highlight the possibility that cumulative, chronic stress effects may nevertheless cause declines in performance for some individuals (leading to lack of improvement in mean time to solve the second maze). If so, this may represent a pervasive but difficult challenge for our ability to robustly estimate learning rates in studies of animal cognition.

MDMA treatment paired with a trauma-cue promotes adaptive stress responses in a translational model of PTSD in rats

MDMA (3,4-methylenedioxymethamphetamine), a synthetic ring-substituted amphetamine, combined with psychotherapy has demonstrated efficacy for the treatment of chronic posttraumatic stress disorder (PTSD) patients. This controlled prospective study aimed to assess the bio-behavioral underpinnings of MDMA in a translational model of PTSD. Rats exposed to predator-scent stress (PSS) were subjected to a trauma-cue at day 7 shortly after single-dose MDMA injection (5 mg/kg). The elevated plus maze and acoustic startle response tests were assessed on day 14 and served for classification into behavioral response groups. Freezing response to a further trauma-reminder was assessed on Day 15. The morphological characteristics of the dentate gyrus (DG) and basolateral amygdala (BLA) were subsequently examined. Hypothalamic–pituitary–adrenal axis and 5-hydroxytryptamine involvement were evaluated using: (1) corticosterone measurements at 2 h and 4 h after MDMA treatment, (2) Lewis strain rats with blunted HPA-response and (3) pharmacological receptor-blockade. MDMA treatment was effective in attenuating stress behavioral responses only when paired with memory reactivation by a trauma-cue. The effects of the treatment on behavior were associated with a commensurate normalization of the dendritic cytoarchitecture of DG and BLA neurons. Pretreatment with RU486, Ketanserin, or Pindolol prevented the above improvement in anxiety-like behavioral responses. MDMA treatment paired with memory reactivation reduced the prevalence rate of PTSD-phenotype 14 days later and normalized the cytoarchitecture changes induced by PSS (in dendritic complexities) compared to saline control. MDMA treatment paired with a trauma-cue may modify or update the original traumatic memory trace through reconsolidation processes. These anxiolytic-like effects seem to involve the HPA axis and 5-HT systems.

Molecular and neural basis of pleasant touch sensation

Pleasant touch provides emotional and psychological support that helps mitigate social isolation and stress. However, the underlying mechanisms remain poorly understood. Using a pleasant touch-conditioned place preference (PT-CPP) test, we show that genetic ablation of spinal excitatory interneurons expressing prokineticin receptor 2 (PROKR2), or its ligand PROK2 in sensory neurons, abolishes PT-CPP without impairing pain and itch behaviors in mice. Mutant mice display profound impairments in stress response and prosocial behaviors. Moreover, PROKR2 neurons respond most vigorously to gentle stroking and encode reward value. Collectively, we identify PROK2 as a long-sought neuropeptide that encodes and transmits pleasant touch to spinal PROKR2 neurons. These findings may have important implications for elucidating mechanisms by which pleasant touch deprivation contributes to social avoidance behavior and mental disorders.

The relation of neuroticism to physiological and behavioral stress responses induced by auditory startle.

IntroductionThe negative cognitive effects of the startle response are not yet fully understood. Ecological observations in the aviation field indicate risk for severe outcomes in complex or pressured situations, while sparse previous research suggests milder negative effects on simple cognitive tasks. Neuroticism is proposed as a factor related to the level of negative effects following startle.MethodsThis study examined the effects of startle on performance in a choice reaction time task and analyzed relations between performance, neuroticism, and physiological stress.ResultsOur results indicate that reaction time directly following startle was not affected, but reaction time in subsequent trials was significantly slower. Neuroticism and physiological stress were both unrelated to this performance effect.DiscussionWe argue that higher complexity/demand tasks are necessary to complement the research on base cognitive functioning in relation to startle. If neuroticism is related to startle effects, this is more likely to be found in these higher demand situations.

Emotion regulation and cortisol response to the still-face procedure in preterm and full-term infants

In infancy, stress responses and emotion regulation are often coupled. Both are impacted by prematurity, though their relationship to one another in the case of infants born preterm is not fully understood. We investigated emotion regulation behaviours, cortisol reactivity and recovery and coupling between emotion regulation and cortisol reactivity to and recovery from a stressor in preterm infants. 53 preterm and 67 full-term infants with mean (range) gestational age at birth 29+3 (24+0-31+6) and 39+3 (36+2-42+0) weeks respectively were exposed to a socio-emotional stressor, the still-face (SF) paradigm, at 9 months of age (corrected for prematurity). The duration of negative affect and self-comforting behaviours exhibited in response to the SF, coded from a 10-minute video-taped interaction, were compared between groups. Saliva was collected from a subset (20 preterm, 24 term infants) at three timepoints: pre-SF and 20- and 30-minutes post SF. Cortisol concentrations at each timepoint were compared between groups. Associations between behavioural measures and cortisol concentrations were explored. There was no significant difference in duration of self-comforting behaviour between preterm and term infants. Preterm infants spent a significantly smaller proportion of time in a negative affective state compared to term infants (0.18 vs 0.25 s, p = 0.03). Salivary cortisol concentration was significantly higher in the preterm compared to the term group 30 min post SF (2.85 vs 1.77 nmol/L, p = 0.009), though findings were no longer significant after adjusting for time of day of sampling and socioeconomic deprivation. After controlling for time of day, greater negative affect was correlated with higher cortisol concentration 30 min post SF in the full-term (r = 0.58, p = 0.004) but not the preterm group (r = −0.01, p > 0.05). Our findings suggest altered response to an acute stressor in preterm infants, manifesting as a muted emotional response, and a lack of coupling between endocrine and behavioural stress response. Replication studies in larger samples would help to further understand biological stress repose in preterm infants and its relationship to behaviour, time of day and deprivation.

Alone but not always lonely: Social cues alleviate isolation induced behavioural stress in wild zebrafish

Social isolation has been routinely used for experimental studies on many animal model systems. Additionally, considering the recent increase in the prevalence of isolation in the human population, it has become even more imperative to understand social isolation and measures that might alleviate its effects. Using wild-caught zebrafish, our study aims to elucidate the effect of social cues on reducing behavioural stress caused due to acute social isolation in a socially aggregating species. Fish were kept in groups or individually, with either visual and olfactory cues, only visual cues or no social cues, and tested for behavioural stress every alternate day in a commonly used open tank test. Experimental observations measured a range of behavioural indicators of stress such as geotaxis (ratio of time spent in top half of the tank to time spent in the bottom half of the tank), thigmotaxis (average duration of visit to wall of tanks), activity (homogeneity and extent) and freezing (average duration of freezing bout) among individuals that were kept in differing levels of social isolation. We found that the presence of both visual and olfactory cues from conspecifics significantly decreased stress in individuals as compared to only visual cues being present. Fish that were completely isolated showed significant increase in stress levels, as indicated by all observed indicators of behavioural stress. Over trials, except for completely isolated individuals, fish showed an eventual decrease in stress levels, indicating acclimatisation. Males and females showed differences in behavioural stress, with females exhibiting a lower baseline stress level, as well as less response to isolation. Our findings not only demonstrate the importance of social cues in managing stress when social isolation is unavoidable, but also add to the knowledge about behavioural stress response measures in zebrafish, which is an important vertebrate model used to extrapolate information about stress and anxiety in humans as well.

Deformation mechanism and cyclic stress response of Zircaloy-4 alloy cladding tube during low cycle fatigue at room temperature

This work systematically investigated the deformation mechanism and cyclic stress response behavior of Zircaloy-4 alloy cladding tube at room temperature. Low cyclic fatigue tests revealed that cyclic softening and hardening strongly depend on the applied strain amplitude. Besides, prismatic < a > slip was the primary cyclic deformation mode when the value of plastic strain amplitude less than that of elastic strain amplitude, otherwise prismatic < a > slip and {101¯2} <1¯011 > twinning dominated the deformation. Due to the combination effect of grain rotation, dislocation accumulation and twinning, cyclic softening, saturation and hardening behaviors were presented in Zircaloy-4 alloy.

Cross-fostering alters the post-weaning pig behavioral stress response in a sex-specific manner

The purpose of the current study was to evaluate whether early postnatal stress due to cross-fostering alters the behavioral response to stress in weaned pigs. We hypothesized that piglets who were cross-fostered (FOS) into another existing litter would exhibit heightened behavioral indicators of stress after weaning in response to three behavioral stress tests compared to their non-biological litter mates (NBL), and their non-fostered biological siblings (CON). Three FOS piglets from each CON litter (n = 11 litters) were randomly selected and moved to a foster litter (n = 11 litters) 12–24 h post-farrowing, where they were nursed along NBL piglets until weaning (approximately 18 d of age). At 7- and 14-d post-weaning, all piglets underwent a novel object test (NOT) in their home pens. At 21- and 28-d post-weaning, one male and one female piglet from each treatment (CON, FOS, NBL) underwent one of two behavioral tests: social isolation and dyadic contest in an isolated 1.22 × 1.22 m novel pen. All data were analyzed using the GLIMMIX procedure in SAS. Non-biological littermate pigs exhibited a lower latency to interact with a novel object during NOT round 1 compared to CON pigs (P = 0.02), whereas FOS pigs were intermediate to but not different from either treatment (P > 0.05). A treatment by sex interaction was detected during NOT round 2 (P = 0.004), where FOS males exhibited a lower latency to interact with a novel object compared to CON pigs and FOS female pigs. Additionally, NBL females exhibited a lower latency to interaction with a novel object during NOT round 2 compared to CON, FOS female, and NBL male pigs. No treatment differences were detected during the social isolation test (P > 0.05). Treatment by sex interactions were detected during the dyadic contest for number of aggressive interactions (P < 0.01) and number of aggressive interactions initiated by an opponent (P < 0.01). Specifically, CON females and FOS males received a greater number of aggressive interactions and a greater number of aggressive interactions initiated by an opponent compared to CON males, FOS females, and NBL pigs. Taken together, these results indicate that the early postnatal stress associated with cross-fostering affects FOS piglets in a sex-specific manner. Further, NBL pigs may be the most capable of handling novel stressors post-weaning, as they exhibited fewer behavioral indicators of stress during the NOT and dyadic contests.

TIP60 buffers acute stress response and depressive behaviour by controlling PPARγ-mediated transcription

Tat-interacting protein 60 (TIP60) as nuclear receptors (NRs) coregulator, acts as a tumor suppressor and also has promising therapeutic potential to target Alzheimer’s disease. Stress has been implicated in many psychiatric disorders, and these disorders are characterized by impairments in cognitive function. Until now, there are no experimental data available on the regulatory effect of TIP60 in acute stress and depression. There is also no definitive explanation on which specific modulation of target gene expression is achieved by TIP60. Here, we identify TIP60 as a novel positive regulator in response to acute restraint stress (ARS) and a potentially effective target of antidepressants. Firstly, we discovered increased hippocampal TIP60 expressions in the ARS model. Furthermore, using the TIP60 inhibitor, MG149, we proved that TIP60 function correlates with behavioral and synaptic activation in the two-hour ARS. Secondly, the lentivirus vector (LV)-TIP60overexpression (OE) was injected into the hippocampus prior to the chronic restraint stress (CRS) experiments and it was found that over-expressed TIP60 compensates for TIP60 decrease and improves depression index in CRS. Thirdly, through the intervention of TIP60 expression in vitro, we established the genetic regulation of TIP60 on synaptic proteins, confirmed the TIP60 function as a specific coactivator for PPARγ and found that the PPARγ-mediated TIP60 function modulates transcriptional activation of synaptic proteins. Finally, the LV-TIP60OE and PPARγ antagonist, GW9662, were both administered in the CRS model and the data indicated that blocking PPARγ significantly weakened the protective effect of TIP60 against the CRS-induced depression. Conclusively, these findings together support TIP60 as a novel positive factor in response to acute stress and interacts with PPARγ to modulate the pathological mechanism of CRS-induced depression.