Early maternal deprivation predisposes adult rats to colonic mucosal barrier dysfunction in response to mild stress

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.

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

AJP Gastrointestinal and Liver Physiology ◽

10.1152/ajpgi.00392.2006 ◽

2007 ◽

Vol 293 (1) ◽

pp. G198-G203 ◽

Cited By ~ 95

Author(s):

Mélanie G. Gareau ◽

Jennifer Jury ◽

Mary H. Perdue

Keyword(s):

Maternal Separation ◽

Mucosal Barrier ◽

Epithelial Barrier ◽

Epithelial Permeability ◽

Barrier Dysfunction ◽

Adult Rats ◽

Western Blots ◽

Ussing Chambers ◽

Rat Pups ◽

Neonatal Maternal Separation

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.

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Sodium Butyrate Functions as an Antidepressant and Improves Cognition with Enhanced Neurotrophic Expression in Models of Maternal Deprivation and Chronic Mild Stress

Current Neurovascular Research ◽

10.2174/1567202611666140829162158 ◽

2014 ◽

Vol 11 (4) ◽

pp. 359-366 ◽

Cited By ~ 36

Author(s):

Samira Valvassori ◽

Roger Varela ◽

Camila Arent ◽

Gustavo Dal-Pont ◽

Tamara Bobsin ◽

...

Keyword(s):

Sodium Butyrate ◽

Chronic Mild Stress ◽

Maternal Deprivation ◽

Mild Stress

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Early life maternal deprivation attenuates morphine induced inhibition in lateral paragigantocellularis neurons in adult rats

Brain Research Bulletin ◽

10.1016/j.brainresbull.2021.01.011 ◽

2021 ◽

Vol 169 ◽

pp. 128-135

Author(s):

Hossein Masrouri ◽

Maryam Azadi ◽

Saeed Semnanian ◽

Hossein Azizi

Keyword(s):

Early Life ◽

Maternal Deprivation ◽

Adult Rats

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Gut Mucosal Barrier Dysfunction, Microbial Dysbiosis, and Their Role in HIV-1 Disease Progression

The Journal of Infectious Diseases ◽

10.1093/infdis/jiw258 ◽

2016 ◽

Vol 214 (suppl 2) ◽

pp. S58-S66 ◽

Cited By ~ 73

Author(s):

Joseph C. Mudd ◽

Jason M. Brenchley

Keyword(s):

Disease Progression ◽

Mucosal Barrier ◽

Barrier Dysfunction ◽

Microbial Dysbiosis ◽

Gut Mucosal Barrier ◽

Hiv 1

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Gut relief formula attenuates dextran sulfate sodium-induced colitis by regulating NF-κB signaling and the intestinal microbiota in mice

Food & Function ◽

10.1039/d1fo01477c ◽

2021 ◽

Author(s):

Xuemeng Si ◽

Ning Liu ◽

Hai Jia ◽

Jiaqi Wang ◽

Lina Pan ◽

...

Keyword(s):

Intestinal Microbiota ◽

Dextran Sulfate ◽

Dextran Sulfate Sodium ◽

Mucosal Barrier ◽

Mucosal Inflammation ◽

Barrier Dysfunction

Gut relief formula administration alleviated mucosal inflammation and mucosal barrier dysfunction by inhibiting STAT3 and NF-κB activity and upregulating abundances of Lactobacillus in DSS-induced colitis.

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Alterations of the Predominant Fecal Microbiota and Disruption of the Gut Mucosal Barrier in Patients with Early-Stage Colorectal Cancer

BioMed Research International ◽

10.1155/2020/2948282 ◽

2020 ◽

Vol 2020 ◽

pp. 1-8 ◽

Cited By ~ 4

Author(s):

Xia Liu ◽

Yiwen Cheng ◽

Li Shao ◽

Zongxin Ling

Keyword(s):

Colorectal Cancer ◽

Diamine Oxidase ◽

Early Stage ◽

Fusobacterium Nucleatum ◽

Fecal Microbiota ◽

Mucosal Barrier ◽

Beneficial Bacteria ◽

Barrier Dysfunction ◽

Real Time Quantitative Pcr ◽

Gut Mucosal Barrier

Growing evidence indicated that the gut microbiota was the intrinsic and essential component of the cancer microenvironment, which played vital roles in the development and progression of colorectal cancer (CRC). In our present study, we investigated the alterations of fecal abundant microbiota with real-time quantitative PCR and the changes of indicators of gut mucosal barrier from 53 early-stage CRC patients and 45 matched healthy controls. We found that the traditional beneficial bacteria such as Lactobacillus and Bifidobacterium decreased significantly and the carcinogenic bacteria such as Enterobacteriaceae and Fusobacterium nucleatum were significantly increased in CRC patients. We also found gut mucosal barrier dysfunction in CRC patients with increased levels of endotoxin (LPS), D-lactate, and diamine oxidase (DAO). With Pearson’s correlation analysis, D-lactate, LPS, and DAO were correlated negatively with Lactobacillus and Bifidobacterium and positively with Enterobacteriaceae and F. nucleatum. Our present study found dysbiosis of the fecal microbiota and dysfunction of the gut mucosal barrier in patients with early-stage CRC, which implicated that fecal abundant bacteria and gut mucosal barrier indicators could be used as targets to monitor the development and progression of CRC in a noninvasive and dynamic manner.

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Chloride channels regulate differentiation and barrier functions of the mammalian airway

eLife ◽

10.7554/elife.53085 ◽

2020 ◽

Vol 9 ◽

Cited By ~ 2

Author(s):

Mu He ◽

Bing Wu ◽

Wenlei Ye ◽

Daniel D Le ◽

Adriane W Sinclair ◽

...

Keyword(s):

Chloride Channels ◽

Mucociliary Clearance ◽

Mucosal Barrier ◽

Barrier Dysfunction ◽

Genetic Inactivation ◽

Airway Diseases ◽

Conducting Airway ◽

Molecular Events ◽

And Function ◽

Human Fetal Development

The conducting airway forms a protective mucosal barrier and is the primary target of airway disorders. The molecular events required for the formation and function of the airway mucosal barrier, as well as the mechanisms by which barrier dysfunction leads to early onset airway diseases, remain unclear. In this study, we systematically characterized the developmental landscape of the mouse airway using single-cell RNA sequencing and identified remarkably conserved cellular programs operating during human fetal development. We demonstrated that in mouse, genetic inactivation of chloride channel Ano1/Tmem16a compromises airway barrier function, results in early signs of inflammation, and alters the airway cellular landscape by depleting epithelial progenitors. Mouse Ano1-/-mutants exhibited mucus obstruction and abnormal mucociliary clearance that resemble the airway defects associated with cystic fibrosis. The data reveal critical and non-redundant roles for Ano1 in organogenesis, and show that chloride channels are essential for mammalian airway formation and function.

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