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Tight junction proteins in the small intestine and prefrontal cortex of female rats exposed to stress of chronic isolation starting early in life
Author(s) -
Karailiev Peter,
Hlavacova Natasa,
Chmelova Magdalena,
Homer Natalie Z. M.,
Jezova Daniela
Publication year - 2021
Publication title -
neurogastroenterology and motility
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.489
H-Index - 105
eISSN - 1365-2982
pISSN - 1350-1925
DOI - 10.1111/nmo.14084
Subject(s) - prefrontal cortex , claudin , endocrinology , medicine , mineralocorticoid receptor , occludin , chronic stress , intestinal permeability , anxiogenic , blockade , tight junction , spironolactone , blood–brain barrier , barrier function , biology , receptor , aldosterone , neuroscience , microbiology and biotechnology , central nervous system , anxiolytic , cognition
Background Simultaneous evaluation of barrier protein expression in the gut and the brain and their modulation under stress conditions have not been studied before now. As the permeability and function of the gut and blood‐brain barrier are different and both express the MRs, we hypothesized that stress of post‐weaning social isolation induces changes in tight junction protein expression in the gut which are (1) independent of changes in the brain and (2) are mediated via the mineralocorticoid receptor (MR). Methods First, using UPLC‐MS/MS we have successfully validated and selected a dose (1.2 mg/rat/day) of the MR antagonist spironolactone to treat female rats exposed to stress of chronic isolation or control conditions from postnatal day 21 for 9 weeks. Key Results Isolation stress caused an enhancement of gene expression of occludin and ZO‐1 and a decrease in claudin‐5 and MR expression in both the small intestine and prefrontal cortex. Isolation stress failed to decrease claudin‐5 (small intestine) and MR (prefrontal cortex) gene expression in spironolactone‐treated rats. MR blockade resulted in a decrease in claudin‐15 expression in the small intestine. Anxiogenic effect of chronic stress, measured in elevated plus‐maze test, was partly prevented by spironolactone treatment. Conclusions & Inferences Claudins, the main regulators of intestinal barrier permeability responded to chronic stress of social isolation and/or simultaneous blockade of MR in female rats by alterations independent of changes in the brain cortex. The results suggest a physiological role of MR in the control of claudin expression in the small intestine, but not in the brain cortex.