Effects of postnatal social isolation on hormonal and immune responses of pigs to an acute endotoxin challenge

Forschungsbereich Verhaltensphysiologie, Forschungsinstitut für die Biologie landwirtschaftlicher Nutztiere, Wilhelm-Stahl-Allee 2, D-18196, Dummerstorf, Germany.
Physiology & Behavior (Impact Factor: 2.98). 10/2004; 82(2-3):503-11. DOI: 10.1016/j.physbeh.2004.04.056
Source: PubMed


Social stress during early postnatal life often results in long-term effects on neuroendocrine and immune adaptation mechanisms. Therefore, the aim of the present study was to determine the influence of a 2-h daily social isolation from Day 3 to Day 11 on the acute and long-term proinflammatory and neuroendocrine responses of piglets challenged with the bacterial endotoxin lipopolysaccharide (LPS; 100 microg/kg body weight). Peripheral LPS administration significantly increased plasma concentrations of tumor necrosis factor-alpha (TNF-alpha), ACTH and cortisol in isolated and control pigs. However, the activity of the hypothalamic-pituitary-adrenal (HPA) axis after LPS stimulation was not significantly affected by isolation treatment, whereas the prior social isolation diminished the plasma TNF-alpha response to LPS 1 day as well as 45 days after the isolation period. The hippocampal TNF-alpha concentration in response to LPS was also reduced in priorly isolated pigs compared to control animals. Furthermore, the significant increase of TNF-alpha in the spleen caused by LPS was associated with a dramatic decrease in glucocorticoid receptor (GR) binding. The GR binding in hippocampus was increased in isolated pigs and was significantly decreased after LPS injection. In addition, the repeated isolation stressor was shown to increase hippocampal levels of interleukin-1beta (IL-1beta). The present results indicate that repeated social isolation of neonatal pigs may cause long-term effects on proinflammatory regulation at the periphery and in the brain following immune challenge with particular importance of TNF-alpha in mediating these interactions.

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    • "Pig Early weaning Maternal separation Stress-related gene expression in brain Neuroendocrine responses Immunological responses Kanitz et al. (2004), Tuchscherer et al. (2004, 2006 "
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    ABSTRACT: Early origins of adult disease may be defined as adversity or challenges during early life that alter physiological responses and prime the organism to chronic disease in adult life. Adverse childhood experiences or early life stress (ELS) may be considered a silent independent risk factor capable of predicting future cardiovascular disease risk. Maternal separation (MatSep) provides a suitable model to elucidate the underlying molecular mechanisms by which ELS increases the risk to develop cardiovascular disease in adulthood. The aim of this review is to describe the links between behavioural stress early in life and chronic cardiovascular disease risk in adulthood. We will discuss the following: (i) adult cardiovascular outcomes in humans subjected to ELS, (ii) MatSep as an animal model of ELS as well as the limitations and advantages of this model in rodents and (iii) possible ELS-induced mechanisms that predispose individuals to greater cardiovascular risk. Overall, exposure to a behavioural stressor early in life sensitizes the response to a second stressor later in life, thus unmasking an exaggerated cardiovascular dysfunction that may influence quality of life and life expectancy in adulthood.
    Full-text · Article · Oct 2013 · Acta Physiologica
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    • "Despite the fact that their need for these social strategies is practically eliminated in captivity, social animals still become stressed by isolation (Andersen et al., 2006). For example, young pigs especially show behavioural and physiological signs of stress when housed in isolation such as increased cortisol production (Ruis et al., 2001; Stolba and Wood-Gush, 1989), decreased body temperature (Ruis et al., 2001), decreased Tumour Necrosis Factor-alpha (TNF-␣) (Tuchscherer et al., 2004), and increased frequency of behaviours associated with anxiety and stress (Herskin and Jensen, 2000; Tuchscherer et al., 2006). Similarly, housing within barren environments may also modify pigs' behaviour and physiology. "
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    ABSTRACT: Pigs may be housed individually in both production and research settings. Gregarious by nature, pigs kept in isolation may show behavioural and physiological signs of stress. In this study we investigated the preference of individually housed pigs, for social and non-social enrichments. Three enrichment items were compared: a mat (MAT), a companion (COM) and a mirror (MIR). Fourteen weaner pigs (Yorkshire × Landrace) were housed individually with continuous access to 4 adjacent pens. One pen was a control (CTRL) and had no enrichment; the others had one enrichment each, either a mat on part of the woven wire floor (MAT), a companion visible across the passageway (COM) or a mirror on one wall (MIR). Pigs spent more proportion of time (P = 0.021) in the COM pen (0.65 ± 0.07) compared to the CTRL pen (0.31 ± 0.07) with the MAT pen (0.57 ± 0.07) and the MIR (0.42 ± 0.07) pen as intermediates. They also spent more total time engaged in investigative and inactive behaviours in the COM pen compared to the CTRL pen (P = 0.007). A second analysis was performed to investigate changes in preferences in the presence or absence of a human in the room. The pens were then combined into two categories: social pens (COM and MIR) and nonsocial pens (MAT and CTRL). The probability of a pig being observed in the MIR pen when a human was present was significantly higher (P = 0.0001), than when absent. Within the social enrichments, the probability of the animal being observed in either MIR or COM pen was not different (P = 0.017). Our results confirm that preference studies may be highly sensitive to experimental conditions. Thus, the assumption that the most important preference is the one the animal spends most of its time with can be misleading. It appears that a mirror may be used by the animal for social support during periods of perceived threat, however further investigation is warranted.
    Full-text · Article · Jan 2013 · Applied Animal Behaviour Science
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    • "Typically, early-life stress is linked to adult offspring that exhibit stress hyper-responsiveness due to altered ontogeny of the HPA axis (Kapoor et al., 2006). Perinatal stress results in altered GR and MR expression and function in the brain as well as altered responsivity to stress (Avishai-Eliner et al., 2001; Kapoor et al., 2008; Levitt et al., 1996; Sutanto et al., 1996; Tuchscherer et al., 2004; Vallee et al., 1999). One form of stress commonly experienced in the neonatal period is exposure to bacterial and viral infections. "
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    ABSTRACT: Stressful events during the perinatal period in both humans and animals have long-term consequences for the development and function of physiological systems and susceptibility to disease in adulthood. One form of stress commonly experienced in the neonatal period is exposure to bacterial and viral infections. The current study investigated the effects of live Chlamydia muridarum bacterial infection at birth followed by re-infection in adulthood on hippocampal glucocorticoid receptors (GR) and mineralocorticoid receptors (MR) and stress response outcomes. Within 24 h of birth, neonatal mice were infected intranasally with C. muridarum (400 inclusion-forming units [ifu]) or vehicle. At 42 days, mice were re-infected (100 ifu) and euthanized 10 days later. In males, infection in adulthood alone had the most impact on the parameters measured with significant increases in GR protein compared to adult infection alone; and significant increases MR protein and circulating corticosterone compared to other treatment groups. Neonatal infection alone induced the largest alterations in the females with results showing reciprocal patterns for GR protein and TH protein. Perinatal infection resulted in a blunted response following adult infection for both males and females across all parameters. The present study demonstrates for the first time that males and females respond differently to infection based on the timing of the initial insult and that there is considerable sex differences in the hippocampal phenotypes that emerge in adulthood after neonatal infection.
    Full-text · Article · Mar 2011 · Brain Behavior and Immunity
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