Early social isolation alters behavioral and physiological responses to an endotoxin challenge in piglets

Psychosocial stress in the form of maternal deprivation and social isolation during early postnatal life induces persistent alterations in behavioral and physiological mechanisms of adaptation. One consequence may be an increased susceptibility to diseases in later life. Therefore, the aim of the present study was to investigate in domestic piglets the effects of a repeated social isolation (2 h daily from day 3 to day 11 of age) on behavioral, endocrine and immune responses to an endotoxin challenge with lipopolysaccharide (LPS) 1 day or 45 days after the isolation period. Peripheral LPS administration caused serious sickness behavior (somnolence, shivering, vomiting) and provoked profound increases in circulating tumor necrosis factor-α (TNF-α), ACTH and cortisol concentrations. The prior social isolation treatment enhanced signs of sickness and impaired suckling behavior. Early isolated piglets responded to LPS by an increase of shivering on day 12 and by increased vomiting on day 56 compared to controls. Further, there were considerable delays and reductions of time isolated piglets spent suckling on day 12. The repeated isolation stressor diminished TNF-α increases after LPS, whereas stress hormone levels were not significantly affected by isolation treatment. Finally, stronger relationships between signs of sickness and physiological measures were revealed in early isolated piglets. The duration of somnolence in isolated piglets was related to changes of cortisol and TNF-α concentrations, and the highest impact on duration of shivering was found for changes in cortisol and corticosteroid binding globulin levels. The present results suggest a sustained adaptive sensitization of coping with infection by social stress experience during early development in piglets.     

Early social isolation alters behavioral and physiological responses to an endotoxin challenge in piglets

Psychosocial stress in the form of maternal deprivation and social isolation during early postnatal life induces persistent alterations in behavioral and physiological mechanisms of adaptation. One consequence may be an increased susceptibility to diseases in later life. Therefore, the aim of the present study was to investigate in domestic piglets the effects of a repeated social isolation (2 h daily from day 3 to day 11 of age) on behavioral, endocrine and immune responses to an endotoxin challenge with lipopolysaccharide (LPS) 1 day or 45 days after the isolation period. Peripheral LPS administration caused serious sickness behavior (somnolence, shivering, vomiting) and provoked profound increases in circulating tumor necrosis factor-alpha (TNF-alpha), ACTH and cortisol concentrations. The prior social isolation treatment enhanced signs of sickness and impaired suckling behavior. Early isolated piglets responded to LPS by an increase of shivering on day 12 and by increased vomiting on day 56 compared to controls. Further, there were considerable delays and reductions of time isolated piglets spent suckling on day 12. The repeated isolation stressor diminished TNF-alpha increases after LPS, whereas stress hormone levels were not significantly affected by isolation treatment. Finally, stronger relationships between signs of sickness and physiological measures were revealed in early isolated piglets. The duration of somnolence in isolated piglets was related to changes of cortisol and TNF-alpha concentrations, and the highest impact on duration of shivering was found for changes in cortisol and corticosteroid binding globulin levels. The present results suggest a sustained adaptive sensitization of coping with infection by social stress experience during early development in piglets.     

Rehabilitation of research chimpanzees: stress and coping after long-term isolation

We report on the permanent retirement of chimpanzees from biomedical research and on resocialization after long-term social isolation. Our aim was to investigate to what extent behavioral and endocrine measures of stress in deprived laboratory chimpanzees can be improved by a more species-typical social life style. Personality in terms of novelty responses, social dominance after resocialization and hormonal stress susceptibility were affected by the onset of maternal separation of infant chimpanzees and duration of deprivation. Chimpanzees, who were separated from their mothers at a younger age and kept in isolation for more years appeared to be more timid personalities, less socially active, less dominant and more susceptible to stress, as compared to chimpanzees with a less severe deprivation history. However, permanent retirement from biomedical research in combination with therapeutic resocialization maximizing chimpanzees' situation control resulted in reduced fecal cortisol metabolite levels. Our results indicate that chimpanzees can recover from severe social deprivation, and may experience resocialization as less stressful than solitary housing.     

Deprivation of maternal care has long-lasting consequences for the hypothalamic-pituitary-adrenal axis of zebra finches

Early-life stress caused by the deprivation of maternal care has been shown to have long-lasting effects on the hypothalamic-pituitary-adrenal (HPA) axis in offspring of uniparental mammalian species. We asked if deprivation of maternal care in biparental species alters stress responsiveness of offspring, using a biparental avian species--the zebra finch, Taeniopygia guttata. In our experiment, one group of birds was raised by both male and female parents (control), and another was raised by males alone (maternally deprived). During adulthood, offspring of both groups were subjected to two stressors (restraint and isolation), and corticosterone concentrations were measured. Additionally, we measured baseline levels of the two corticosteroid receptors--glucocorticoid receptor (GR) and mineralocorticoid receptor (MR)--in the hippocampus, hypothalamus and cerebellum. Our results suggest that maternally deprived offspring are hyper-responsive to isolation in comparison with controls. Furthermore, mRNA levels of both GR and MR receptors are altered in maternally deprived offspring in comparison with controls. Thus, absence of maternal care has lasting consequences for HPA function in a biparental species where paternal care is available.     

Gonadectomy negatively impacts social behavior of adolescent male primates

Social behavior changes dramatically during primate adolescence. However, the extent to which testosterone and other gonadal hormones are necessary for adolescent social behavioral development is unknown. In this study, we determined that gonadectomy significantly impairs social dominance in naturalistic settings and changes reactions to social stimuli in experimental settings. Rhesus macaques were castrated (n =  6) or sham operated (n = 6) at age 2.4 years, group-housed for 2 years, and ethograms were collected weekly. During adolescence the gonadally intact monkeys displayed a decrease in subordinate behaviors and an increase in dominant behaviors, which ultimately related to a rise in social status and rank in the dominance hierarchy. We measured monkey's reactions to emotional faces (fear, threat, neutral) of conspecifics of three ages (adult, peer, infant). Intact monkeys were faster to retrieve a treat in front of a threatening or infant face, while castrated monkeys did not show a differential response to different emotional faces or ages. No group difference in reaction to an innate fear-eliciting object (snake) was found. Approach and proximity responses to familiar vs unfamiliar conspecifics were tested, and intact monkeys spent more time proximal to a novel conspecific as compared to castrates who tended to spend more time with a familiar conspecific. No group differences in time spent with novel or familiar objects were found. Thus, gonadectomy resulted in the emergence of significantly different responses to social stimuli, but not non-social stimuli. Our work suggests that intact gonads, which are needed to produce adolescent increases in circulating testosterone, impact social behavior during adolescences in primates.     

Social context and reaction to separation in peer-reared pigtail macaques: Some preliminary observations

The social environment affects both behavioral and physiological responses to separation from the mother. Less information is available on the impact of the social environment on the response to separation in peer-reared infant monkeys. This study reports the responses of peer-reared pigtail macaque infants to repeated separations, and the impact of social versus isolation housing during the separation. The responses of two pairs of monkeys were studied during four three-day separations. One of each pair was housed in isolation during the separation, and the other was with another pair of peers, with whom they had been living for one month prior to the separation. The isolation-housed peer responded to the separation with behavioral agitation, but no depression. The socially-housed peer's behavior did not differ from baseline during the separation. During successive reunions, all the separated monkeys, regardless of housing condition, exhibited declining levels of behaviors related to maintaining proximity to their attachment figure. Although the number of subjects is small, the results suggest that the presence of social support, in the form of a familiar peer, can ameliorate the response to separation, and that with repeated separations the responses of the monkeys changes significantly.     

Maternal Deprivation Induces Depressive-like Behaviour and Alters Neurotrophin Levels in the Rat Brain

The present study was aimed to evaluate the behavioral and molecular effects of maternal deprivation in adult rats. To this aim, male rats deprived and non-deprived were assessed in the forced swimming and open-field tests in adult phase. In addition adrenocorticotrophin hormone (ACTH) levels was assessed in serum and brain-derived-neurotrophic factor (BDNF), neurotrophin-3 (NT-3) and nerve growth factor (NGF) protein levels were assessed in prefrontal cortex, hippocampus and amygdala. We observed that maternal deprivation increased immobility time, and decreased climbing time, without affecting locomotor activity. ACTH circulating levels were increased in maternal deprived rats. Additionally, BDNF protein levels were reduced in the amygdala and NT-3 and NGF were reduced in both hippocampus and amygdala in maternal deprived rats, compared to control group. In conclusion, our results support the idea that behavioral, ACTH circulating levels and neurotrophins levels altered in maternal deprivation model could contribute to stress-related diseases, such as depression.     

Temperament moderates the influence of periadolescent social experience on behavior and adrenocortical activity in adult male rats

Adolescence is a period of significant behavioral and physiological maturation, particularly related to stress responses. Animal studies that have tested the influence of adolescent social experiences on stress-related behavioral and physiological development have led to complex results. We used a rodent model of neophobia to test the hypothesis that the influence of adolescent social experience on adult behavior and adrenocortical function is modulated by pre-adolescent temperament. Exploratory activity was assessed in 53 male Sprague–Dawley rats to classify temperament and then they were housed in one of the three conditions during postnatal days (PND) 28–46: (1) with familiar kin, (2) with novel social partners, or (3) individually with no social partners. Effects on adult adrenocortical function were evaluated from fecal samples collected while rats were individually-housed and exposed to a 1-hour novel social challenge during PND 110–114. Adolescent-housing with novel or no social partners led to reduced adult glucocorticoid production compared to adolescent-housing with familiar littermates. Additionally, highly-exploratory pre-weanling rats that were housed with novel social partners during adolescence exhibited increased exploratory behavior and a more rapid return to basal glucocorticoid production in adulthood compared to those housed with familiar or no social partners during adolescence and compared to low-exploratory rats exposed to novel social partners. In sum, relatively short-term adolescent social experiences can cause transient changes in temperament and potentially longer-term changes in recovery of glucocorticoid production in response to adult social challenges. Furthermore, early temperament may modulate the influence of adolescent experiences on adult behavioral and adrenocortical function.     

Vocal buffering of the stress response: exposure to conspecific vocalizations moderates urinary cortisol excretion in isolated marmosets

For many species, the presence of a significant social partner can lessen the behavioral and physiological responses to stressful stimuli. This study examined whether a single, individually specific, signature vocalization (phee call) could attenuate the physiological stress response that is induced in marmosets by housing them in short-term social isolation. Utilizing a repeated-measures design, adult marmosets (n=10) were temporarily isolated from their long-term pair mate and exposed to three conditions: signature vocalizations from the pair mate, phee calls from an unfamiliar opposite sex individual, or no auditory stimuli. Levels of urinary cortisol were monitored as a physiological indicator of the stress response. Urinary cortisol levels were also monitored, while subjects remained undisturbed in their home cages to provide baseline levels. Temporarily isolated marmosets showed significantly higher levels of urinary cortisol than undisturbed marmosets. However, the nature of the acoustic stimulus experienced during isolation led to differences in the excretion of urinary cortisol. Isolated marmosets exposed to a familiar pair mate's vocalization showed significantly lower levels of urinary cortisol than when exposed to unfamiliar marmoset vocalizations (P <0.04) or to no auditory stimuli (P <0.03). Neither the duration of pairing nor the quality of relationship in the pair (indexed by spatial proximity scores) predicted the magnitude of reduction in cortisol in the familiar vocalization condition. The results presented here provide the first evidence that a single, individually specific communication signal can decrease the magnitude of a physiological stress response in a manner analogous to the physical presence of a social partner, a process we term "vocal buffering."     

The influence of domestic piglets' (<Emphasis Type="Italic">Sus scrofa</Emphasis>) age and test experience on the preference for the replayed maternal nursing vocalisation in a modified open-field test

The nursing vocalisation of lactating sows is an important part of the complex nursing and suckling behaviour of domestic pigs (Sus scrofa). It helps to lead the young through the several phases of a nursing episode. A total of 135 suckling piglets were investigated regarding their reactions to different vocalisations and sounds successively replayed in combined choice/open-field experiments. Two piglet samples were used to determine the impact of age (sample 1: weeks 1 and 5, n=93) and previous test experience of naive older piglets (sample 2: week 5, n=42) on their behavioural responses. In the 1st week after birth, the nursing vocalisation of sows released an initial generalised approach and contact response in the young, indicating high motivation to gain nutritional or social support. Close to the sound source, the piglets then strongly preferred the nursing vocalisation produced by their own mothers compared to that produced by another, unrelated and unfamiliar sow, or an artificial sound composed of similar frequencies as the nurse grunting, or a control without sound. However, at the end of the suckling period (5-week-old piglets) no clear differences in the reactions to the sounds could be identified. Moreover, the lack of a clear response at week 5 seems largely independent of any earlier test experience of the piglets. As well in the 1st as in the 5th week the piglets showed a decrease in open-field activity when sow grunting was present, indicating that the replay of the nursing vocalisation might have some calming effect. Communicated by K. Kotrschal     

Changes in social environment induce higher emotional disturbances than changes in physical environment in quail

In intensive rearing, birds are exposed to frequent changes in both their social and physical environments, and this can have an impact on animal welfare under commercial conditions. The aim of the present study was to compare the emotional responses induced by social and non-social changes and to study the influence of the familiarity on these responses.Twenty-two female quail were first reared with a ball in 15–20-individual groups for 3 weeks from hatching. Then, each experimental subject was allocated either a familiar congener (CONG) or a familiar object (BALL). At 6 weeks of age the birds were fitted with a telemetric device to collect motor and cardiac activities. After that, each subject was exposed first to a separation from its cage-mate/familiar object, and secondly to the (re-)introduction of either the cage-mate/familiar object or of an unknown conspecific/another ball. Emotional responses were assessed through behavioural reactions and heart rate variability.Before being separated, both BALL and CONG quail showed stereotyped pacing that was more pronounced in BALL quail. BALL quail were not affected by the ball withdrawal, unlike CONG quail which reacted to the separation from their cage-mate by reducing activity and exploratory behaviour (P < 0.05). After the re-introduction, BALL quail remained closer to their ball and CONG quail spent more time with “stretched necks” than before the separation (P < 0.05). Surprisingly, CONG quail showed less stereotyped pacing when their partner was removed and recovered the initial level of stereotyped behaviour when their cage-mate was re-introduced (P < 0.01). Likewise, CONG quail also recovered the initial values of heart rate after the re-introduction of their cage-mate, indicating an increase in sympathetic activity compared to the isolation period. When the unfamiliar congener or ball was introduced in their cage, BALL quail pecked the unknown ball more than the familiar ball and had more contact with it (P < 0.05) and CONG quail had more contact with the unknown congener than with the cage-mate (P < 0.05).In conclusion, the quail appeared to experience a negative affective state before being separated, and there was no clear evidence of negative emotion in quail in response to the separation from either a social partner or an inanimate object. Nevertheless, the emotional responses of the quail in reaction to the (re-)introduction was influenced by the familiarity of the congener or the ball. Finally, changes in the quail's social environment induced more behavioural and cardiac modifications than changes in its non-social environment.     

Effects of Passive Social Support in Juvenile Greylag Geese (Anser anser): A Study from Fledging to Adulthood

In general, support by social allies may reduce stress, increase an individual's status and facilitate access to resources. In Greylag geese (Anser anser), offspring stay with their parents for an entire year or even longer and thereby enjoy social support in encounters with other flock members. We investigated the influence of spatial distance to one's allies on the outcome of agonistic encounters in a natural flock situation for a total of 12 sibling groups after fledging. In addition, we tested two groups of hand‐raised juvenile geese over a time span of 11/2 yr. Passive (i.e. not interfering) human supporters of different familiarity were placed at a standard distance during food provisionings, which produced a tight flock situation. Success in agonistic interactions increased with decreasing distance to members of their social unit. The hand‐raised juveniles were more successful in agonistic interactions and showed increased feeding rates when accompanied by a familiar human than when alone or with a non‐familiar human. The effect of the presence of familiar humans on success in agonistic encounters significantly decreased with increasing age, while feeding rates remained elevated. The positive effects of social support were particularly evident in females. We conclude that social support has similar effects and functions in the highly social greylag geese as reported for social mammals.     

Social buffering reduces male rats' behavioral and corticosterone responses to a conditioned stimulus

In social species, the presence of an affiliative same-sex conspecific ameliorates acute stress responses in threatening conditions. We previously found that the presence of an unfamiliar male rat separated by a wire mesh barrier blocks the behavioral responses and Fos expression in the paraventricular nucleus of the hypothalamus (PVN) in a male subject rat that had previously been exposed to an auditory conditioned stimulus (CS) paired with foot shocks. Based on the Fos expression in the PVN, we hypothesized that the presence of a conspecific ameliorated the hypothalamic–pituitary–adrenal (HPA) axis activation and induced social buffering of conditioned fear responses. The direct evidence for this hypothesis, however, is still lacking. To clarify this point, we exposed fear-conditioned and non-conditioned subjects to the CS either alone or with a conspecific separated by a wire mesh barrier. When the fear-conditioned subject alone was re-exposed to the CS, it exhibited increased freezing, decreased sniffing, and elevated corticosterone levels. In contrast, the presence of the conspecific suppressed these behavioral and HPA axis responses to a level similar to those observed in the non-conditioned subjects. These results suggest that the presence of a conspecific suppressed the behavioral responses and HPA axis activation to the CS. The present results provide direct evidence for the existence of social buffering of conditioned fear responses in male rats.     

Socio-economic disparities in the burden of seasonal influenza: the effect of social and material deprivation on rates of influenza infection

Background

There is little empirical evidence in support of a relationship between rates of influenza infection and level of material deprivation (i.e., lack of access to goods and services) and social deprivation (i.e. lack of social cohesion and support).

Method

Using validated population-level indices of material and social deprivation and medical billing claims for outpatient clinic and emergency department visits for influenza from 1996 to 2006, we assessed the relationship between neighbourhood rates of influenza and neighbourhood levels of deprivation using Bayesian ecological regression models. Then, by pooling data from neighbourhoods in the top decile (i.e., most deprived) and the bottom decile, we compared rates in the most deprived populations to the least deprived populations using age- and sex-standardized rate ratios.

Results

Deprivation scores ranged from one to five with five representing the highest level of deprivation. We found a 21% reduction in rates for every 1 unit increase in social deprivation score (rate ratio [RR] 0.79, 95% Credible Interval [CrI] 0.66, 0.97). There was little evidence of a meaningful linear relationship with material deprivation (RR 1.06, 95% CrI 0.93, 1.24). However, relative to neighbourhoods with deprivation scores in the bottom decile, those in the top decile (i.e., most materially deprived) had substantially higher rates (RR 2.02, 95% Confidence Interval 1.99, 2.05).

Conclusion

Though it is hypothesized that social and material deprivation increase risk of acute respiratory infection, we found decreasing healthcare utilization rates for influenza with increasing social deprivation. This finding may be explained by the fewer social contacts and, thus, fewer influenza exposure opportunities of the socially deprived. Though there was no evidence of a linear relationship with material deprivation, when comparing the least to the most materially deprived populations, we observed higher rates in the most materially deprived populations.     

Long-term effects of adolescent stress on neophobic behaviors in zebra finches are modulated by social context when in adulthood

Experiencing stress during adolescence can increase neophobic behaviors in adulthood, but most tests have been conducted in the absence of conspecifics. Conspecifics can modulate responses to stressors, for example by acting as ‘social buffers’ to attenuate the aversive appraisal of stressors. Here, we investigate the long-term effects of adolescent stress on the behavioral responses to novel stimuli (a mild stressor) across social contexts in an affiliative passerine bird, the zebra finch. During early (days 40–60) or late (days 65–85) adolescence the birds (n = 66) were dosed with either saline or the hormone corticosterone (CORT). CORT was given in order to mimic a physiological stress response and saline was given as a control. In adulthood, the birds' behavioral responses to a novel environment were recorded in both the presence and absence of conspecifics. An acute CORT response was also quantified in adolescence and adulthood. Our findings show clear evidence of social context mediating any long-term effects of adolescent stress. In the presence of familiar conspecifics no treatment effects were detected. Individually, birds dosed with CORT in early adolescence were slower to enter a novel environment, spent more time perching in the same novel environment, and, if female, engaged in more risk assessment. Birds dosed in late adolescence were unaffected. No treatment effects were detected on CORT, but adolescents had a higher CORT concentration than adults. Our results are the first to suggest that familiar conspecifics in adulthood can buffer the long-term effects of stress that occurred during early adolescence.     

Effects of soybean glycinin on performance and immune function in early weaned pigs

Glycinin, a major storage protein in soybean, has been identified as an important food allergen. The present study was conducted to investigate the effects of soybean glycinin on the local and systemic immune responses using a swine model specific for glycinin allergy. Performance, peripheral blood lymphocyte proliferation and CD4+ and CD8+ subsets in the plasma of naive and sensitised piglets were determined. In addition, the concentrations of IgA, IgG, IgM, interleukin-4 and interleukin-6 in the jejunum mucosa were measured. Our results showed that dietary supplementation of glycinin reduced piglet performance (p < 0.05), while increasing lymphocyte proliferation and CD4+/ CD8+ ratio (p < 0.01). Intestinal mucosal immune responses to glycinin were enhanced with high levels of IgA (p < 0.01) as well as interleukin-4 and interleukin-6 in the jejunum mucosa in glycinin-treated piglets compared with the control (p < 0.01). There were no differences due to treatment in the densities of IgG and IgM. In conclusion, it was found that glycinin stimulated local and systemic immune responses in allergic piglets and had negative effects on piglet performance. The severity of the immune reactions depends on the dose of glycinin with higher doses causing more severe symptoms.     

Social reinstatement responses of meat-type chickens to familiar and unfamiliar conspecifics after exposure to an acute stressor

Runway tests are considered indicative of underlying sociality in birds and their ability to make social discriminations. We evaluated whether experience of a prior stressor alters the subsequent affiliation responses of 9 or 10-day-old chicks simultaneously exposed to familiar (cagemates) and unfamiliar conspecifics placed in goal boxes at opposite ends of a runway. Birds were housed in groups of eight in home cages. Half of the birds in each home cage were used as either familiar or unfamiliar social stimuli in the goal boxes. The other half of the birds were randomly assigned either to a control (CON; n = 51) group that remained undisturbed until testing or to a stress-treatment (STR; n = 52) group that was exposed to a 5-min restraint stressor, returned to its home cage and then tested 1 h later. Birds were individually tested in the runway for 5 min and the behaviours video-recorded. During revision of tapes, the projected floor image of the runway was divided into squares and zones. The stressor decreased (P < 0.01) the time spent in close proximity (close zone; CZ) to conspecifics regardless of the familiarity of the stimulus birds. Regardless of treatment, test chicks showed shorter latencies to enter (P < 0.05) and spent longer time (P < 0.02) in the familiar than in the unfamiliar CZ suggesting that young chicks can discriminate between familiar and unfamiliar conspecifics encountered in novel surroundings. While in close proximity to familiar conspecifics, STR birds showed a reduced (P < 0.05) number of squares entered compared to CONs. This reduced locomotor activity was not accompanied by an increased activity in other zones of the runway. At the end of the trial, both CON and STR birds showed a reduced (P < 0.05) locomotor activity in the unfamiliar CZ and an increased (P < 0.05) activity in the central zone of the runway. Interestingly, no differences were detected between CON and STR birds in the total number of squares entered during the trial. These results suggest that prior stressor exposure did not affect the overall amount of locomotion but altered the spatial distribution of it. Collectively, our findings suggest that exposure to an acute stressor event subsequently affects chicks’ affiliation responses in runway tests. The way a bird will react depends on the identity (familiar or unfamiliar) of the conspecifics in its close environment.     

Neonatal paternal deprivation impairs social recognition and alters levels of oxytocin and estrogen receptor α mRNA expression in the MeA and NAcc,and serum oxytocin in mandarin voles

Paternal care is necessary for the healthy development of social behavior in monogamous rodents and social recognition underpins social behavior in these animals. The effects of paternal care on the development of social recognition and underlying neuroendocrine mechanisms, especially the involvement of oxytocin and estrogen pathways, remain poorly understood. We investigated the effects of paternal deprivation (PD: father was removed from neonatal pups and mother alone raised the offspring) on social recognition in mandarin voles (Microtus mandarinus), a socially monogamous rodent. Paternal deprivation was found to inhibit the development of social recognition in female and male offspring according to a habituation–dishabituation paradigm. Paternal deprivation resulted in increased inactivity and reduced investigation during new encounters with other animals. Paternal deprivation reduced oxytocin receptor (OTR) and estrogen receptor α (ERα) mRNA expression in the medial amygdala and nucleus accumbens. Paternal deprivation reduced serum oxytocin (OT) concentration in females, but had no effect on males. Our results provide substantial evidence that paternal deprivation inhibits the development of social recognition in female and male mandarin voles and alters social behavior later in life. This is possibly the result of altered expression of central OTR and ERα and serum OT levels caused by paternal deprivation.