Stress signaling pathways activated by weaning mediate intestinal dysfunction in the pig

Abstract

Weaning in the piglet is a stressful event associated with gastrointestinal disorders and increased disease susceptibility. Although stress is thought to play a role in postweaning intestinal disease, the mechanisms by which stress influences intestinal pathophysiology in the weaned pig are not understood. The objectives of these experiments were to investigate the impact of weaning on gastrointestinal health in the pig and to assess the role of stress signaling pathways in this response. Nineteen-day-old pigs were weaned, and mucosal barrier function and ion transport were assessed in jejunal and colonic tissues mounted on Ussing chambers. Weaning caused marked disturbances in intestinal barrier function, as demonstrated by significant ( P < 0.01) reductions in transepithelial electrical resistance and increases in intestinal permeability to [3H]mannitol in both the jejunum and colon compared with intestinal tissues from age-matched, unweaned control pigs. Weaned intestinal tissues exhibited increased intestinal secretory activity, as demonstrated by elevated short-circuit current that was sensitive to treatment with tetrodotoxin and indomethacin, suggesting activation of enteric neural and prostaglandin synthesis pathways in weaned intestinal tissues. Western blot analyses of mucosal homogenates showed increased expression of corticotrophin-releasing factor (CRF) receptor 1 in the jejunum and colon of weaned intestinal tissues. Pretreatment of pigs with the CRF receptor antagonist α-helical CRF(9–41), which was injected intraperitoneally 30 min prior to weaning, abolished the stress-induced mucosal changes. Our results indicate that weaning stress induces mucosal dysfunction mediated by intestinal CRF receptors and activated by enteric nerves and prostanoid pathways.

Invited review: Aspects of gastrointestinal tract growth and maturation in the pre- and postweaning period of pigs

“…While feed intake level after weaning affects small intestinal structure and function (Kelly et al, 1991;Pluske et al, 1996a,b), the effect on intestinal barrier function is less consistent, and it is most likely that additional stress (maternal separation, mixing with unfamiliar littermates, and change in environment) coupled with starvation compromises intestinal barrier function (McCracken et al, 1999). In this regard, Moeser et al (2007b) linked weaning stress and the corticotropin-releasing factor (CRF) signaling pathways to GIT dysfunction, demonstrating that weaning (at 19 d of age) caused an immediate breakdown of intestinal barrier function that was characterized by a reduction in transepithelial electrical resistance and increased paracellular [ 3 H] mannitol flux. These changes in the mucosa were mediated by activation of peripheral CRF receptors commensurate with inflammatory responses, mast cell activation, and the release of some proinflammatory cytokines and can be modulated by a delay in the weaning age (Moeser et al, 2007a).…”

Effect of weaning age on cortisol release in piglets

“…Most studies that have investigated cortisol levels in piglets have only examined levels at a single-weaning age (Moeser et al, 2007;Campbell et al, 2013;Wu et al, 2013;Fang et al, 2014;Liu et al, 2014;Wang et al, 2014). A few have explored the effects of different weaning ages on cortisol levels (Colson et al, 2006;Jarvis et al, 2008), but none have studied the effect of weaning age on the adrenal cortex.…”

Jejunal morphology and blood metabolites in tail biting, victim and control pigs

“…This may be a consequence of a stressful environment or decreased feed intake in tail-biting pens, which we were unable to measure. It is possible that endocrine secretion in stressful conditions may have an effect on the jejunal surface (Moeser et al, 2007). In the work by Yu et al (2010), increased cortisol concentrations were associated with decreased villus height and crypt depth during and after heat stress.…”