ABSTRACT
Early-life adversity may have programming effects on the psychological and physiological development of offspring. Domestic pigs (Sus scrofa) 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). Control piglets (C) from 10 sows stayed with their mothers. Mother-offspring interaction, milk oxytocin, and cortisol were analyzed. An open-field/novel-object (OF/NO) test was performed with piglets on PNDs 16 and 40. Plasma cortisol and immune parameters were determined on PND 5 and 16. Two piglets from each group and sow were sacrificed on PND 20 and stress-related gene expression in the limbic system and prefrontal cortex (PFC), as well as splenic lymphocyte proliferative abilities, were examined. The milk cortisol of sows increased during the first separation of mother and offspring on the second day of lactation, whereas milk oxytocin did not change. The increase in cortisol by the OF/NO test on PND 16 was greater in C piglets than in DA and DG ones. DA piglets showed less agitated behavior than DG and C piglets in the OF/NO test at PND 16, but appeared more fearful. On PND 40, DA piglets showed more arousal than DG and C piglets in the OF/NO test. Neither plasma IgA nor N/L ratios in blood nor mitogen-induced proliferation of spleen lymphocytes were affected by deprivation. We found a higher mRNA expression of CRHR1 in the hypothalamus and a higher expression of MR in the hippocampus in DA piglets than in DG ones. The expression of GR, MR, and CRHR1 genes in the PFC was reduced by maternal deprivation, however, the expression of arginine vasopressin and oxytocin receptors was not affected. Repeated maternal deprivation induces sustained effects on stress reactivity and behavior of domestic piglets. Some of these effects were buffered by the presence of littermates. In addition, we found sex-specific differences in behavior and gene expression.
ABSTRACT
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. DA+DG piglets showed stronger signs of sickness compared to control (C) piglets. Plasma TNF-α concentrations were significantly lower in DA+DG males. In addition, the TNF-α/IL-10 ratio was significantly lower in DA than in DG and C males. Gene expression analyses showed lower hypothalamic TNF-α mRNA expression and diminished mRNA expression of the mineralocorticoid receptor (MR) and IL-10 in the amygdala of DA+DG piglets in response to LPS. Interestingly, males showed a higher MR- and a lower IL-10 mRNA expression in the amygdala than females. The present data suggest that repeated maternal deprivation during early life may alter neuroendocrine and immune responses to acute endotoxaemia in a sex-specific manner.