Mild postnatal separation stress reduces repeated stress-induced immunosuppression in adult BALB/c mice.

OBJECTIVES: Different inbred mouse strains but also each animal of the same strain show an individually different stress response which is influenced by genetic and environmental factors such as early life experiences. In this study, we investigated consequences of mild postnatal stress exposure on the stress coping style of adult BALB/c mice. METHODS: We used a model of mild early life stress where neonatal mice were repeatedly separated from the dam staying with their siblings for 1-h each day during the first two postnatal weeks. The environment during maternal separation was adapted to the nest (bedding, 37 degrees C warm). RESULTS: Adult female BALB/s mice that underwent the maternal separation protocol or were not isolated from the dam in early life were exposed to combined acoustic and restraint stress in adulthood. Repeated maternal separation which was performed under ambient conditions increased the stress coping ability of mice at the age of 12 weeks when exposed to this psychological stressors. By acoustic and restraint stress-induced alterations such as high corticosterone levels, an anti-inflammatory immune conditioning with an ex vivo hyperinducibility of interleukin-10 of splenocytes and a massive loss of body weight were significantly reduced in the maternally separated group compared with conventionally bred control mice. CONCLUSIONS: Mild maternal separation in early life modifies the stress coping style of adult female BALB/c mice to a more stress-resistant phenotype which shows reduced repeated stress-induced immune suppression and weight loss and is linked to reduced release of glucocorticoids after stress exposure.

Postnatal life events affect the severity of asthmatic airway inflammation in the adult rat.

Genetic and hygienic factors influence susceptibility to asthma. In autoimmune and inflammatory diseases, additional effects of the psychosocial environment have been demonstrated that might also play a role in asthma. In this study, the impact of different early postnatal stressors on an OVA-induced model of asthma was tested in adulthood. Fischer 344 rats were subjected to either repeated handling stimulation (HA), maternal separation (MS), or were left undisturbed in their first 4 wk of life. Behavioral differences were characterized at the age of 4 mo. At 5 mo of age, immunological cellular and serologic changes were investigated and experimental asthma was induced. Results show significantly increased exploratory behavior and reduced anxiety in HA rats compared with MS and controls. Without further behavioral or immunological challenges, HA animals exhibited an increased ex vivo NK cell cytotoxicity but no other obvious immunological differences. After induction of asthma, in contrast, MS animals exhibited proinflammatory effects in leukocyte subset composition including increased eosinophil numbers, whereas levels of IgE and the allergy-specific cytokine IL-13 were reduced compared with HA. There was a most remarkable increase of adrenocorticotropin in HA animals, comparing pre- to postchallenge plasma levels. These data demonstrate for the first time that early postnatal stimulative or adverse experiences exert long-lasting changes of the "neuroendocrinoimmune" interface in adulthood, resulting in either protective or aggravating mechanisms in allergic airway disease. Thus, in addition to genetic and hygienic factors, nongenetically acquired individual differences contribute to the pathobiology of asthma.

Maternal separation disrupts the integrity of the intestinal microflora in infant rhesus monkeys.

The integrity of the indigenous microflora of the intestines after maternal separation was investigated in infant rhesus monkeys to determine whether psychological stress may lead to an internal environment conducive to pathogen infection. The stability of the indigenous microflora were estimated by enumeration of total and gram-negative aerobic and facultatively anaerobic bacterial species, specifically Lactobacilli, from coprocultures taken before and after maternal separation. In addition, behavioral and cortisol responses to separation were correlated to the microflora. A significant decrease in fecal bacteria, especially Lactobacilli, was evident on day 3 postseparation, with a return to baseline by the end of the week. The drop in the microflora was correlated with the display of stress-indicative behaviors, but not with cortisol secretion. In addition, infants who displayed numerous stress-indicative behaviors were more susceptible to opportunistic bacterial infection. These results suggest that strong emotional reactions to disruption of the mother-infant bond may increase vulnerability to disease.

Intrinsic and extrinsic factors affect infant responses to maternal separation.

Responses of individuals to the loss of a primary attachment object may be quite variable. In humans, it has been suggested that only about 25% of bereavements result in substantial psychological or medical morbidity (Hamburg et al. 1975). In nonhuman primates, which are used to model responses to separation and loss, a similar estimate of about 25% has also been obtained (McKinney 1985). In addition, there are wide-ranging species differences in vulnerability with regard to the nature and severity of the response to maternal separation and/or loss. All of these findings suggest that there are important processes, intrinsic and/or extrinsic to the individual, that contribute to the probability that a loss will produce a major behavioral or physiological response. We have been systematically examining some of the factors that may account for a portion of this variability in two species of macaques (bonnet monkeys Macaca radiata; and pigtail monkeys, M. nemestrina).

Removal from natal social group to peer housing affects cortisol levels and absolute numbers of T cell subsets in juvenile rhesus monkeys.

Psychosocial stress associated with the removal of six naive juvenile rhesus monkeys from their natal social group to peer housing resulted in increased basal cortisol secretion and significant decrements in the absolute numbers of the T lymphocyte subsets in the peripheral blood. Six subjects matched for age and social rank remained in the group of 80 animals serving as controls. Baseline immune and cortisol measurements were obtained before the six test subjects were removed from the group and housed together in an outdoor circular enclosure. Blood samples were taken 24 h following removal of the test subjects from the group and at intervals thereafter through 11 weeks. Compared to controls, test subjects showed a significant decrease in the absolute numbers of CD4+ (-56.9%) and CD8+ T cells (-57.6%) and a significant increase in basal cortisol levels (+43.9%) 24 h following removal to peer housing. Group difference in the absolute numbers of most immune cells persisted through 11 weeks, whereas cortisol differences lasted only through 2 weeks. These data, when compared to an earlier study employing an identical protocol, with the exception that subjects were housed in indoor individual cages following separation, fail to demonstrate a modulating effect of randomly chosen peer-mates on the stress effects produced by social separation.