Early-life maternal deprivation affects the mother-offspring relationship in domestic pigs, as well as the neuroendocrine development and coping behavior of piglets.

Early-life adversity may have programming effects on the psychological and physiological development of offspring. Domestic pigs () are an excellent model species for studying these effects because of their many physiological similarities to humans. Piglets from 10 sows were subjected to daily 2-h maternal deprivation on postnatal days (PND) 2-15 alone (DA) or in a group of littermates (DG).

A natural Ala610Val substitution causing glucocorticoid receptor hypersensitivity aggravates consequences of endotoxemia.

Despite the crucial role of glucocorticoid receptor (GR) in proper immune responses, the effect of GR hypersensitivity on inflammation is rarely reported. To fill this knowledge gap, we exploited the natural gain-of-function substitution in the porcine glucocorticoid receptor (GR) and challenged pigs carrying normal or hypersensitive GR using 50 µg/kg lipopolysaccharide (LPS) following pretreatment with either saline or single bolus of 60 µg/kg dexamethasone (DEX). The GR substitution reduced baseline cortisol, adrenocorticotropic hormone (ACTH), and triglyceride concentration and granulocyte proportion whereas baseline platelet counts were elevated.

Early-Life Maternal Deprivation Predicts Stronger Sickness Behaviour and Reduced Immune Responses to Acute Endotoxaemia in a Pig Model.

Early-life adversity may have programming effects on neuroendocrine and immune adaptation mechanisms in humans and socially living animals. Using a pig model, we investigated the effect of daily 2-h maternal and littermate deprivation from postnatal days 2-15, either alone (DA) or in a group of littermates (DG) on the neuroendocrine, immunological and behavioural responses of piglets challenged with the bacterial endotoxin lipopolysaccharide (LPS) on day 42. LPS increased plasma concentrations of cortisol, tumour necrosis factor-alpha (TNF-α), interleukin-6 (IL-6) and interleukin-10 (IL-10) and induced typical signs of sickness in all piglets.

Coping Style of Pigs Is Associated With Different Behavioral, Neurobiological and Immune Responses to Stressful Challenges.

Based on the animal's reaction to environmental challenges, consistent but different coping styles can be identified, which in turn may have consequences for health and welfare. Therefore, profound knowledge of the complex interrelationships between individual behavioral response patterns, underlying neurobiological mechanisms and immunological effects is required. The aim of this study was to examine whether pigs with different coping styles exhibit distinct behavioral, neurobiological and immune responses to stressful situations.

Kinetics of Physiological and Behavioural Responses in Endotoxemic Pigs with or without Dexamethasone Treatment.

Although dexamethasone (DEX) is a widely used immunoregulatory agent, knowledge about its pharmacological properties in farm animals, especially pigs, is insufficient. Previous studies suggest that compared to other species, pigs are less sensitive to the immunosuppression conferred by DEX and more sensitive to the threat of bacterial endotoxins. However, there is a paucity of studies examining DEX immunomodulation in endotoxemia in this species.

Effects of 1-Methyltryptophan on Immune Responses and the Kynurenine Pathway after Lipopolysaccharide Challenge in Pigs.

An enhanced indoleamine 2,3-dioxygenase 1 (IDO1) activity is associated with an increased mortality risk in sepsis patients. Thus, the preventive inhibition of IDO1 activity may be a promising strategy to attenuate the severity of septic shock. 1-methyltryptophan (1-MT) is currently in the interest of research due to its potential inhibitory effects on IDO1 and immunomodulatory properties.

Psychosocial Stress and Immunity-What Can We Learn From Pig Studies?

Psychosocial stress may impair immune functions and provoke the development of pathologies. The underlying communication between the brain and the immune system is being studied predominantly in rodents. However, pigs offer several advantages as preclinical models for humans because pigs are more similar to humans than rodents in many anatomical and physiological characteristics.

Sea Buckthorn Pomace Supplementation in the Diet of Growing Pigs-Effects on Fatty Acid Metabolism, HPA Activity and Immune Status.

There is evidence that sea buckthorn, as a source of -3 polyunsaturated fatty acids (-3 PUFA), possesses health-enhancing properties and may modulate neuroendocrine and immune functions. In the present study, we investigated the effect of sea buckthorn pomace (SBP) supplementation in the diet of growing German Landrace pigs on fatty acids in the blood and hypothalamus, peripheral immune parameters and mRNA expression of corticotropin-releasing hormone (CRH), mineralocorticoid receptor (MR) and glucocorticoid receptor (GR) in the hypothalamus and spleen. Pigs were fed diets supplemented with 12% of dried SBP or 0% SBP (control group) over an intervention period of eight weeks.

Psychosocial stress sensitizes neuroendocrine and inflammatory responses to Escherichia coli challenge in domestic piglets.

Exposure to psychosocial stress can have a profound impact on immune reactivity and health mediated by hypothalamic-pituitaryadrenal (HPA) axis activation. However, current knowledge regarding the mechanisms involved in cross-sensitization between stress and the immune system is limited. Here, we investigated the effects of a single social isolation followed by repeated oral Escherichia coli (E.

Interference of stress with the somatotropic axis in pigs - lights on new biomarkers.

The acceptance of animal products is increasingly associated with standardized animal welfare, which relates to appropriate animal husbandry from birth to slaughter. In particular, shipment to the slaughterhouse is considered as a critical process exposing the animals to a number of, in part severe, stressors. New biomarkers may be useful for the assessment of animal welfare.

Social Support Modulates Stress-Related Gene Expression in Various Brain Regions of Piglets.

The presence of an affiliative conspecific may alleviate an individual's stress response in threatening conditions. However, the mechanisms and neural circuitry underlying the process of social buffering have not yet been elucidated. Using the domestic pig as an animal model, we examined the effect of a 4-h maternal and littermate deprivation on stress hormones and on mRNA expression of the glucocorticoid receptor (GR), mineralocorticoid receptor (MR), 11ß-hydroxysteroid dehydrogenase (11ß-HSD) types 1 and 2 and the immediate early gene c-fos in various brain regions of 7-, 21- and 35-day old piglets.

Effects of social support on glucocorticoid sensitivity of lymphocytes in socially deprived piglets.

There is growing evidence that social support given by a conspecific attenuates stress responses of a socially deprived animal. We hypothesized that the presence of a familiar social partner modulates the effectiveness of social buffering as assessed by an altered glucocorticoid sensitivity of immune cells. The current study investigated the effects of a 4-h social deprivation procedure on stress hormone responses and immune cell functions in 7-, 21- and 35-day-old piglets (52 males and 56 females).

Pharmacokinetics of 1-methyl-L-tryptophan after single and repeated subcutaneous application in a porcine model.

Increased activity of the tryptophan-metabolizing enzyme indoleamine 2,3-dioxygenase (IDO) is associated with immunological and neurological disorders, and inhibition of its enzyme activity could be a therapeutic approach for treatment of these disorders. The aim of the present study was to establish a large animal model to study the accumulation of the potential IDO inhibitor 1-methyltryptophan (1-MT) in blood and different organs of domestic pigs (Sus scrofa domestica). Because 1-MT has not been previously evaluated in pigs, the pharmacokinetics of a single subcutaneous 1-MT application was investigated.

Social support modulates splenocyte glucocorticoid sensitivity in piglets exposed to social deprivation stress.

There is growing evidence that positive social interactions can attenuate the effects of stressful life experiences. However, little is known about the benefits of social partners on stress responses in farm animals. Therefore, in this study we examined the effects of social support on the endocrine and immune stress responses to a single 4h social deprivation in domestic piglets at 7, 21 or 35days of age.

Social support attenuates the adverse consequences of social deprivation stress in domestic piglets.

Social deprivation is a severe stressor affecting a number of behavioral and physiological functions of gregarious species. It is assumed that, dependent upon the level of familiarity, social support given by a conspecific may attenuate the adverse consequences of stress. We investigated the effects of a 4h maternal and littermate deprivation on behavioral reactions, stress hormone responses and brain corticosteroid receptor expression in 7-, 21- and 35-day-old domestic piglets (Sus scrofa) that were left alone or in the presence either of a familiar or unfamiliar age-matched piglet.

Activation of indoleamine 2,3-dioxygenase by LPS in a porcine model.

Indoleamine 2,3-dioxygenase (IDO) is a rate-limiting enzyme for the degradation of tryptophan (Trp) along the kynurenine (Kyn) pathway, and its increased activation is associated with immunologic disorders. Because the specific role of IDO activation is not yet completely clear, the aim of the present study was to establish a pig model of IDO activation for further research. The activation of IDO in pigs was induced experimentally by LPS stimulation in vivo and ex vivo.

High and low protein∶ carbohydrate dietary ratios during gestation alter maternal-fetal cortisol regulation in pigs.

Imbalanced maternal nutrition during gestation can cause alterations of the hypothalamic-pituitary-adrenal (HPA) system in offspring. The present study investigated the effects of maternal low- and high-protein diets during gestation in pigs on the maternal-fetal HPA regulation and expression of the glucocorticoid receptor (GR), mineralocorticoid receptor (MR), 11β-hydroxysteroid dehydrogenase 1 and 2 (11β-HSD1 and 11β-HSD2) and c-fos mRNAs in the placenta and fetal brain. Twenty-seven German Landrace sows were fed diets with high (HP, 30%), low (LP, 6.

Effects of inadequate maternal dietary protein:carbohydrate ratios during pregnancy on offspring immunity in pigs.

Background: Inadequate nutrition in utero may retard foetal growth and alter physiological development of offspring. This study investigated the effects of low and high protein diets fed to primiparous German Landrace sows throughout pregnancy on the immune function of their offspring at different ages. Sows were fed diets with adequate (AP, 12.

Tumour necrosis factor receptor deficiency alters anxiety-like behavioural and neuroendocrine stress responses of mice.

Tumour necrosis factor (TNF)-alpha is known to be involved in anxiety and the regulation of the hypothalamic-pituitary-adrenal axis. To examine the role of its receptors in neuroendocrine immunomodulation, we studied behaviour, corticosterone production and T-cell activation in mice with a C57BL/6J background and deficient for one or both TNF receptors (TNFR1-/-, TNFR2-/-, and TNFR1+2-/-) compared to wildtype C57BL/6J mice with and without psychological stress. Stress was induced by social disruption (SDR), and anxiety-like behaviour was examined using the elevated plus maze (EPM).

Intrauterine growth retarded progeny of pregnant sows fed high protein:low carbohydrate diet is related to metabolic energy deficit.

High and low protein diets fed to pregnant adolescent sows led to intrauterine growth retardation (IUGR). To explore underlying mechanisms, sow plasma metabolite and hormone concentrations were analyzed during different pregnancy stages and correlated with litter weight (LW) at birth, sow body weight and back fat thickness. Sows were fed diets with low (6.

Alterations in anxiety-like behavior following knockout of the uncoupling protein 2 (ucp2) gene in mice.

Aims: Uncoupling protein 2 (UCP2) is a mitochondrial protein that reduces oxidative stress and has a protective function in chronic inflammatory diseases such as multiple sclerosis, rheumatoid arthritis and systemic lupus erythematosus. UCP2 is strongly expressed in areas implicated in the central regulation of stress and anxiety. Therefore, we compared the neuroendocrine regulation of stress responses, immunity and behavior in UCP2-deficient and wildtype C57BL/6J mice under psychological stress.

Age-related changes in corticosteroid receptor expression and monoamine neurotransmitter concentrations in various brain regions of postnatal pigs.

Negative early life experience may be associated with altered functioning of stress-related systems and may increase vulnerability to diseases later in life. Corticosteroids are important mediators of homeostasis and stress and exert their effects via two receptors, the mineralocorticoid receptor (MR) and the glucocorticoid receptor (GR), and through the glucocorticoid-metabolizing enzymes 11β-hydroxysteroid dehydrogenase (11β-HSD) types 1 and 2 in a brain-region-specific manner. However, relatively little is known about the postnatal ontogeny of these receptors and enzymes in the central nervous system.

Altered immunomodulation by glucocorticoids in neonatal pigs exposed to a psychosocial stressor.

Stressful early life experiences can have short- and long-term effects on neuroendocrine and immune mechanisms of adaptation, which are primarily modulated by glucocorticoids. This study aimed to examine how the stress and immune systems interact to cope with psychosocial stress induced by a single social isolation (4 h) in neonatal pigs at 7, 21, or 35 d of age. This social isolation provoked increased plasma ACTH and cortisol concentrations and reduced TNF-α levels but had no significant effect on IL-6 levels.

[Effects of weaning age on behavioural and physiological responses of domestic piglets--a review].

Weaning of farm animals is of biological and economical relevance. Due to economical considerations, the weaning age of piglets (Sus scrofa) has drastically been reduced during the last few years, whereas biological consequences remain ambiguous. This review gives a survey of current international research on weaning and its psychobiological consequences in conventional pig farming.

Changes in endocrine and immune responses of neonatal pigs exposed to a psychosocial stressor.

The aim of the study was to determine the effects of a single social isolation (4h) of piglets on immediate changes in stress hormones and immune responses at 7, 21 or 35 days of age. This social stressor caused an increase in plasma ACTH and cortisol concentrations and a decrease in plasma TNF-alpha. The percentage of CD8+ cells increased and the CD4+ cell percentage decreased, resulting in decreasing CD4+/CD8+ ratio.