Neonatal maternal separation of rat pups results in abnormal cholinergic regulation of epithelial permeability

2007 ◽  
Vol 293 (1) ◽  
pp. G198-G203 ◽  
Author(s):  
Mélanie G. Gareau ◽  
Jennifer Jury ◽  
Mary H. Perdue

Neonatal maternal separation (MS) predisposes adult rats to develop stress-induced mucosal barrier dysfunction/visceral hypersensitivity and rat pups to develop colonic epithelial dysfunction. Our aim was to examine if enhanced epithelial permeability in such pups resulted from abnormal regulation by enteric nerves. Pups were separated from the dam for 3 h/day ( days 4– 20); nonseparated (NS) pups served as controls. On day 20, colonic tissues were removed and mounted in Ussing chambers. Horseradish peroxidase (HRP) flux was used to measure macromolecular permeability. HRP flux was increased in MS versus NS pups. The enhanced flux was inhibited by the cholinergic muscarinic antagonist atropine and the nicotinic antagonist hexamethonium. The cholinergic component was greater in tissues from MS versus NS pups, suggesting that increased cholinergic activity was responsible for the MS elevated permeability. Western blots and immunohistochemistry of colonic tissues demonstrated increased expression of choline acetyltransferase (ChAT) in MS pups, indicating greater synthesis of acetylcholine. Since a previous study indicated that corticotrophin-releasing factor (CRF) mediates barrier dysfunction in MS pups, we examined if the two pathways were linked. In MS tissues, nonselective CRF receptor antagonism inhibited the enhanced flux, and the addition of atropine did not produce further inhibition. Using selective receptor antagonists, we identified that CRF receptor 2 was involved in mediating this effect. These findings suggest that CRF, via CRF receptor 2, acts on cholinergic nerves to induce epithelial barrier dysfunction. Our study provides evidence that MS stimulates synthesis of acetylcholine, which, together with released CRF, creates a condition conducive to the development of epithelial barrier defects.

2002 ◽  
Vol 283 (6) ◽  
pp. G1257-G1263 ◽  
Author(s):  
Johan D. Söderholm ◽  
Derrick A. Yates ◽  
Mélanie G. Gareau ◽  
Ping-Chang Yang ◽  
Glenda MacQueen ◽  
...  

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.


Nutrients ◽  
2019 ◽  
Vol 11 (10) ◽  
pp. 2325 ◽  
Author(s):  
Danielle Cardoso-Silva ◽  
Deborah Delbue ◽  
Alice Itzlinger ◽  
Renée Moerkens ◽  
Sebo Withoff ◽  
...  

Gluten-related disorders include distinct disease entities, namely celiac disease, wheat-associated allergy and non-celiac gluten/wheat sensitivity. Despite having in common the contact of the gastrointestinal mucosa with components of wheat and other cereals as a causative factor, these clinical entities have distinct pathophysiological pathways. In celiac disease, a T-cell mediate immune reaction triggered by gluten ingestion is central in the pathogenesis of the enteropathy, while wheat allergy develops as a rapid immunoglobulin E- or non-immunoglobulin E-mediated immune response. In non-celiac wheat sensitivity, classical adaptive immune responses are not involved. Instead, recent research has revealed that an innate immune response to a yet-to-be-defined antigen, as well as the gut microbiota, are pivotal in the development in this disorder. Although impairment of the epithelial barrier has been described in all three clinical conditions, its role as a potential pathogenetic co-factor, specifically in celiac disease and non-celiac wheat sensitivity, is still a matter of investigation. This article gives a short overview of the mucosal barrier of the small intestine, summarizes the aspects of barrier dysfunction observed in all three gluten-related disorders and reviews literature data in favor of a primary involvement of the epithelial barrier in the development of celiac disease and non-celiac wheat sensitivity.


2008 ◽  
Vol 23 (4) ◽  
pp. 375-385 ◽  
Author(s):  
Daniela Rocha Costa Fóscolo ◽  
Rodrigo Bastos Fóscolo ◽  
Umeko Marubayashi ◽  
Adelina Martha Reis ◽  
Cândido Celso Coimbra

2001 ◽  
Vol 120 (5) ◽  
pp. A23-A24 ◽  
Author(s):  
Johan D. Soderholm ◽  
Derrick A. Yates ◽  
Glenda Macqueen ◽  
Mary H. Perdue

2000 ◽  
Vol 118 (4) ◽  
pp. A637 ◽  
Author(s):  
Santosh V. Coutinho ◽  
Marciano R. Sablad ◽  
Jerry C. Miller ◽  
Huping Zhou ◽  
Alan Lam ◽  
...  

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