Abstract
Opposing emotional events (negative/trauma or positive/maternal care) during the postnatal period may differentially influence vulnerability to the effects of stress later in life. The development and course of intestinal disorders such as inflammatory bowel disease are negatively affected by persistent stress, but to date the role of positive life events on these pathologies has been entirely unknown. In the present study, the effect of early life beneficial experiences in the development of intestinal dysfunctions, where inflammation and stress stimuli play a primary role, was investigated. As a “positive” experimental model we used adult male rat progeny nursed by mothers whose drinking water was supplemented with moderate doses of corticosterone (CORT) (0.2 mg/ml) during the lactation period. Such animals have been generally shown to cope better with different environmental situations during life. The susceptibility to inflammatory experimental colitis induced by intracolonic infusion of TNBS (2,4,6-trinitrobenzenesulphonic acid) was investigated in CORT-nursed rats in comparison with control rats. This mild increase in maternal corticosterone during lactation induced, in CORT-nursed rats, a long lasting protective effect on TNBS-colitis, characterized by improvements in some indices of the disease (increased colonic myeloperoxidase activity, loss of body weight and food intake) and by the involvement of endogenous peripheral pathways known to participate in intestinal disorder development (lower plasma corticosterone levels and colonic mast cell degranulation, alterations in the colonic expression of both corticotrophin releasing factor/CRF and its receptor/CRH-1R). All these findings contribute to suggesting that the reduced vulnerability to TNBS-colitis in CORT-nursed rats is due to recovery from the colonic mucosal barrier dysfunction. Such long lasting changes induced by mild hormonal manipulation during lactation, making the adult also better adapted to colonic inflammatory stress, constitute a useful experimental model to investigate the etiopathogenetic mechanisms and therapeutic treatments of some gastrointestinal diseases.
Highlights
Life experiences profoundly influence the later development, the structure and function of an organism.This phenomenon, called ‘‘developmental programming,’’ is a process whereby an environmental factor acting during a sensitive or vulnerable developmental period exerts effects that, in some cases, will persist throughout life.Adaptive or maladaptive responses to environmental stressors reflect an animal’s capacity to re-establish temporarily disrupted physiological homeostasis
These findings are in line with evidence that shows that adverse experiences early in life can have implications in the development and the clinical course of human intestinal disorders, including inflammatory bowel disease (IBD) and intestinal bowel syndrome (IBS) [9,10,11], where inflammatory and stress stimuli play primary roles [12,13]
In colitic CORT-nursed rats, the weight loss and reduced food intake were significantly (P,0.01) milder than those observed in colitic control rats (Fig. 1A and B)
Summary
Life experiences profoundly influence the later development, the structure and function of an organism.This phenomenon, called ‘‘developmental programming,’’ is a process whereby an environmental factor acting during a sensitive or vulnerable developmental period exerts effects that, in some cases, will persist throughout life.Adaptive or maladaptive responses to environmental stressors reflect an animal’s capacity to re-establish temporarily disrupted physiological homeostasis. A number of factors contribute to the qualitative nature of these responses such as: the intensity (high or low) and duration (acute or chronic) of stressors, the individual’s ability to initiate an adaptive response, and the phase of the life when the stressor event occurs Concerning the latter point, during postnatal life, a critical period for neuroendocrinological and behavioural development processes, different emotional events (negative/trauma or positive/maternal care) may influence, in opposite ways, vulnerability to the effects of stress later in life, possibly by inducing a persistent sensitization in stressresponsive neural circuits [1,2,3,4,5]. These findings are in line with evidence that shows that adverse experiences early in life can have implications in the development and the clinical course of human intestinal disorders, including inflammatory bowel disease (IBD) and intestinal bowel syndrome (IBS) [9,10,11], where inflammatory and stress stimuli play primary roles [12,13]
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