title: Gastrointestinal dysfunction induced by early weaning is attenuated by delayed weaning and mast cell blockade in pigs.
abstract: 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 [(3)H]mannitol fluxes. Early weaning resulted in reductions in transepithelial electrical resistance and increases in mucosal permeability to [(3)H]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.
authors.affiliation: Center for Comparative Translational and Molecular Research, College of Veterinary Medicine, North Carolina State Univ., 4700 Hillsborough St., Raleigh, NC 27606, USA. ajmoeser@ncsu.edu
authors.forename: Adam J
authors.initials: AJ
authors.lastname: Moeser
authors.forename: Kathleen A
authors.initials: KA
authors.lastname: Ryan
authors.forename: Prashant K
authors.initials: PK
authors.lastname: Nighot
authors.forename: Anthony T
authors.initials: AT
authors.lastname: Blikslager
mesh_terms: D000375:Aging / Q000378:metabolism; D000818:Animals; D015550:Cell Degranulation / Q000187:drug effects; D044682:Colon, Ascending / Q000187:drug effects* / Q000378:metabolism; D003346:Corticotropin-Releasing Hormone / Q000097:blood; D004205:Cromolyn Sodium / Q000494:pharmacology* / Q000627:therapeutic use; D017097:Electric Impedance; D005765:Gastrointestinal Agents / Q000494:pharmacology* / Q000627:therapeutic use; D005767:Gastrointestinal Diseases / Q000201:enzymology / Q000378:metabolism / Q000517:prevention & control* / Q000523:psychology; D006854:Hydrocortisone / Q000097:blood; D007413:Intestinal Mucosa / Q000187:drug effects / Q000378:metabolism; D007419:Intestinal Secretions / Q000378:metabolism; D007583:Jejunum / Q000187:drug effects* / Q000378:metabolism; D008353:Mannitol / Q000378:metabolism; D008407:Mast Cells / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D010539:Permeability; D018019:Receptors, Corticotropin-Releasing Hormone / Q000378:metabolism; D013315:Stress, Psychological / Q000150:complications* / Q000201:enzymology / Q000378:metabolism; D013552:Swine; D013997:Time Factors; D053802:Tryptases / Q000378:metabolism; D015854:Up-Regulation; D014886:Weaning; D000099052:CRF Receptor, Type 1
chemical_list: D005765:Gastrointestinal Agents; D018019:Receptors, Corticotropin-Releasing Hormone; D008353:Mannitol; D000099052:CRF Receptor, Type 1; D003346:Corticotropin-Releasing Hormone; D053802:Tryptases; D004205:Cromolyn Sodium; D006854:Hydrocortisone