scholarly journals Early weaning stress impairs development of mucosal barrier function in the porcine intestine

2010 ◽  
Vol 298 (3) ◽  
pp. G352-G363 ◽  
Author(s):  
Feli Smith ◽  
Jessica E. Clark ◽  
Beth L. Overman ◽  
Christena C. Tozel ◽  
Jennifer H. Huang ◽  
...  
Keyword(s):  
Mast Cells ◽  
Barrier Function ◽  
Life Stress ◽  
Short Circuit ◽  
Short Circuit Current ◽  
Mucosal Barrier ◽  
Early Weaning ◽  
Barrier Dysfunction ◽  
Weaned Pigs ◽  
Mucosal Barrier Function

Early life stress is a predisposing factor for the development of chronic intestinal disorders in adult life. Here, we show that stress associated with early weaning in pigs leads to impaired mucosal barrier function. Early weaning (15- to 21-day weaning age) resulted in sustained impairment in intestinal barrier function, as indicated by reductions in jejunal transepithelial electrical resistance and elevations in mucosal-to-serosal flux of paracellular probes [3H]mannitol and [14C]inulin measured at 5 and 9 wk of age, compared with that shown in late-weaned pigs (23- to 28-day weaning age). Elevated baseline short-circuit current was observed in jejunum from early-weaned pigs and was shown to be mediated via enhanced Cl− secretion. Jejunal barrier dysfunction in early-weaned pigs coincided with increased lamina propria immune cell density particularly mucosal mast cells. The mast cell stabilizer drug sodium cromoglycolate ameliorated barrier dysfunction and hypersecretion in early-weaned pigs, demonstrating an important role of mast cells. Furthermore, activation of mast cells ex vivo with c48/80 and corticotrophin-releasing factor (CRF) in pig jejunum mounted in Ussing chambers induced barrier dysfunction and elevations in short-circuit current that were inhibited with mast cell protease inhibitors. Experiments in which selective CRF receptor antagonists were administered to early-weaned pigs revealed that CRF receptor 1 (CRFr1) activation mediates barrier dysfunction and hypersecretion, whereas CRFr2 activation may be responsible for novel protective properties in the porcine intestine in response to early life stress.

Recovery of mucosal barrier function in ischemic porcine ileum and colon is stimulated by a novel agonist of the ClC-2 chloride channel, lubiprostone

2007 ◽  
Vol 292 (2) ◽  
pp. G647-G656 ◽  
Author(s):  
Adam J. Moeser ◽  
Prashant K. Nighot ◽  
Kory J. Engelke ◽  
Ryuji Ueno ◽  
Anthony T. Blikslager
Keyword(s):  
Tight Junctions ◽  
Barrier Function ◽  
Structural Changes ◽  
Ex Vivo ◽  
Short Circuit ◽  
Mucosal Barrier ◽  
Ileal Mucosa ◽  
Signaling Mechanism ◽  
Ussing Chambers ◽  
Mucosal Barrier Function

Previous studies utilizing an ex vivo porcine model of intestinal ischemic injury demonstrated that prostaglandin (PG)E2 stimulates repair of mucosal barrier function via a mechanism involving Cl− secretion and reductions in paracellular permeability. Further experiments revealed that the signaling mechanism for PGE2-induced mucosal recovery was mediated via type-2 Cl− channels (ClC-2). Therefore, the objective of the present study was to directly investigate the role of ClC-2 in mucosal repair by evaluating mucosal recovery in ischemia-injured intestinal mucosa treated with the selective ClC-2 agonist lubiprostone. Ischemia-injured porcine ileal mucosa was mounted in Ussing chambers, and short-circuit current ( Isc) and transepithelial electrical resistance (TER) were measured in response to lubiprostone. Application of 0.01–1 μM lubiprostone to ischemia-injured mucosa induced concentration-dependent increases in TER, with 1 μM lubiprostone stimulating a twofold increase in TER (ΔTER = 26 Ω·cm2; P < 0.01). However, lubiprostone (1 μM) stimulated higher elevations in TER despite lower Isc responses compared with the nonselective secretory agonist PGE2 (1 μM). Furthermore, lubiprostone significantly ( P < 0.05) reduced mucosal-to-serosal fluxes of 3H-labeled mannitol to levels comparable to those of normal control tissues and restored occludin localization to tight junctions. Activation of ClC-2 with the selective agonist lubiprostone stimulated elevations in TER and reductions in mannitol flux in ischemia-injured intestine associated with structural changes in tight junctions. Prostones such as lubiprostone may provide a selective and novel pharmacological mechanism of accelerating recovery of acutely injured intestine compared with the nonselective action of prostaglandins such as PGE2.

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

2007 ◽  
Vol 292 (1) ◽  
pp. G173-G181 ◽  
Author(s):  
Adam J. Moeser ◽  
Carin Vander Klok ◽  
Kathleen A. Ryan ◽  
Jenna G. Wooten ◽  
Dianne Little ◽  
...  
Keyword(s):  
Signaling Pathways ◽  
Barrier Function ◽  
Short Circuit ◽  
Mucosal Barrier ◽  
Intestinal Barrier Function ◽  
Stressful Event ◽  
Stress Signaling ◽  
Ussing Chambers ◽  
Mucosal Barrier Function ◽  
The Impact

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.

Neonatal maternal separation predisposes adult rats to colonic barrier dysfunction in response to mild stress

2002 ◽  
Vol 283 (6) ◽  
pp. G1257-G1263 ◽  
Author(s):  
Johan D. Söderholm ◽  
Derrick A. Yates ◽  
Mélanie G. Gareau ◽  
Ping-Chang Yang ◽  
Glenda MacQueen ◽  
...  
Keyword(s):  
Maternal Separation ◽  
Acute Stress ◽  
Short Circuit ◽  
Mucosal Barrier ◽  
Transepithelial Transport ◽  
Mild Stress ◽  
Barrier Dysfunction ◽  
Adult Rats ◽  
Ussing Chambers ◽  
Mucosal Barrier Function

Intestinal dysfunction is related to stress and early life events, but the mechanisms are largely unknown. Our aim was to determine whether early trauma predisposes adult rats to intestinal mucosal dysfunction in response to stress. Neonatal Sprague-Dawley rats were individually separated from their mothers for 3 h/day at 4–21 days of age. Between days 80 and 90, separated and control rats were subjected to mild acute stress (30-min water avoidance) or sham stress. Mucosal barrier function and ion transport were assessed in colonic tissues mounted in Ussing chambers. Mild stress increased short-circuit current, conductance, and transepithelial transport of macromolecules in separated rats, while having minimal effects in controls. Pretreatment of the separated rats with a corticotropin-releasing hormone (CRH) antagonist, the peptide α-helical CRH(9–41) injected intraperitoneally 20 min before stress, abolished the stress-induced mucosal changes. Our results indicate that neonatal trauma can induce phenotypic changes in adulthood, including enhanced vulnerability of the gut mucosa to stress via mechanisms involving peripherally located CRH receptors.

Gastrointestinal dysfunction induced by early weaning is attenuated by delayed weaning and mast cell blockade in pigs

2007 ◽  
Vol 293 (2) ◽  
pp. G413-G421 ◽  
Author(s):  
Adam J. Moeser ◽  
Kathleen A. Ryan ◽  
Prashant K. Nighot ◽  
Anthony T. Blikslager
Keyword(s):  
Mast Cell ◽  
Intestinal Mucosa ◽  
Barrier Function ◽  
Electrical Resistance ◽  
Intestinal Barrier ◽  
Transepithelial Electrical Resistance ◽  
Mast Cell Activation ◽  
Mucosal Barrier ◽  
Early Weaning ◽  
Mucosal Barrier Function

Our previous work has demonstrated that weaning at 19 days of age has deleterious effects on mucosal barrier function in piglet intestine that are mediated through peripheral CRF receptor signaling pathways. The objectives of the present study were to assess the impact of piglet age on weaning-associated intestinal dysfunction and to determine the role that mast cells play in weaning-induced breakdown of mucosal barrier function. Nursing Yorkshire-cross piglets were either weaned at 19 days of age (early-weaned, n = 8) or 28 days of age (late-weaned, n = 8) and housed in nursery pens. Twenty-four hours postweaning, segments of midjejunum and ascending colon from piglets within each weaning age group were harvested and mounted on Ussing chambers for measurements of transepithelial electrical resistance and serosal-to-mucosal [3H]mannitol fluxes. Early weaning resulted in reductions in transepithelial electrical resistance and increases in mucosal permeability to [3H]mannitol in the jejunum and colon ( P < 0.01). In contrast, postweaning reductions in intestinal barrier function were not observed in piglets weaned at 28 days of age. Early-weaned piglet intestinal mucosa had increased expression of CRF receptor 1 protein, increased mucosal mast cell tryptase levels, and evidence of enhanced mast cell degranulation compared with late-weaned intestinal mucosa. Pretreatment of piglets with the mast cell stabilizer drug cromolyn, injected intraperitoneally 30 min prior to weaning, abolished the early-weaning-induced intestinal barrier disturbances. Our results indicate that early-weaning stress induces mucosal dysfunction mediated by intestinal mast cell activation and can be prevented by delaying weaning.

II. Stress and intestinal barrier function

2001 ◽  
Vol 280 (1) ◽  
pp. G7-G13 ◽  
Author(s):  
Johan D. Söderholm ◽  
Mary H. Perdue
Keyword(s):  
Barrier Function ◽  
Clinical Course ◽  
Intestinal Barrier ◽  
Mucosal Barrier ◽  
Intestinal Barrier Function ◽  
Barrier Dysfunction ◽  
Novel Treatments ◽  
Mucosal Barrier Function ◽  
Underlying Mechanisms

The influence of stress on the clinical course of a number of intestinal diseases is increasingly being recognized, but the underlying mechanisms are largely unknown. This themes article focuses on recent findings related to the effects of stress on mucosal barrier function in the small intestine and colon. Experiments using animal models demonstrate that various types of psychological and physical stress induce dysfunction of the intestinal barrier, resulting in enhanced uptake of potentially noxious material (e.g., antigens, toxins, and other proinflammatory molecules) from the gut lumen. Evidence from several studies indicates that in this process, mucosal mast cells play an important role, possibly activated via neurons releasing corticotropin-releasing hormone and/or acetylcholine. Defining the role of specific cells and mediator molecules in stress-induced barrier dysfunction may provide clues to novel treatments for intestinal disorders.

Glucagon-Like Peptide-2 Improve Intestinal Mucosal Barrier Function in Aged Rats

2018 ◽  
Vol 22 (6) ◽  
pp. 731-738 ◽  
Author(s):  
Weiying Ren ◽  
Jiayu Wu ◽  
Li Li ◽  
Y. Lu ◽  
Y. Shao ◽  
...  
Keyword(s):  
Barrier Function ◽  
Mucosal Barrier ◽  
Aged Rats ◽  
Intestinal Mucosal Barrier ◽  
Mucosal Barrier Function ◽  
Glucagon Like Peptide
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