Stereotaxic Exposure of the Central Nucleus of the Amygdala to Corticosterone Increases Colonic Permeability and Reduces Nerve-Mediated Active Ion Transport in Rats

Abstract

Background: Irritable bowel syndrome (IBS) is characterized by visceral pain and abnormal bowel habits that are worsened during stress. Evidence also suggests altered intestinal barrier function in IBS. Previously, we demonstrated that stereotaxic application of the stress hormone corticosterone (CORT) onto the central nucleus of the amygdala (CeA) induces colonic hyperalgesia and anxiety-like behavior in a rat model, however the effect on intestinal permeability and mucosal function remain to be evaluated.Methods: Male Fischer 344 rats underwent bilateral stereotaxic implantation of CORT or inert cholesterol (CHOL)-containing micropellets (30 μg) onto the dorsal margin of the CeA. Seven days later, colonic tissue was isolated to assess tissue permeability in modified Ussing chambers via transepithelial electrical resistance (TEER) and macromolecular flux of horseradish peroxidase (HRP). Secretory responses to electrical field stimulation (EFS) of submucosal enteric nerves as well as activation with forskolin were used to assess movements of ions across the isolated colonic tissues. In a separate cohort, colonic histology, and mast cell infiltration was assessed.Key Results: Compared to CHOL-implanted controls, we determined that exposing the CeA to elevated levels of CORT significantly increased macromolecular flux across the colonic epithelial layer without changing TEER. Nerve-mediated but not cAMP-mediated active transport was inhibited in response to elevated amygdala CORT. There were no histological changes or increases in mast cell infiltration within colonic tissue from CORT treated animals.Conclusion and Inferences: These observations support a novel role for the CeA as a modulator of nerve-mediated colonic epithelial function.

TRPV6 deficiency attenuates stress and corticosterone-mediated exacerbation of alcohol-induced gut barrier dysfunction and systemic inflammation

“…Systemic administration of corticosterone in mice ( 20 ) and rats ( 43 ) or local administration to the central nucleus of the amygdala in rats ( 44 ) results in increased mucosal permeability and disruption of gut barrier function. The current study confirms this effect of corticosterone on intestinal mucosal permeability in the ileum and colon.…”

Epigenetic mechanisms underlying stress‐induced visceral pain: Resilience versus vulnerability in a two‐hit model of early life stress and chronic adult stress

“…Since the OAL model does not lead to premature HPA axis activity or abnormal HPA axis activity in adulthood, it is possible that the mechanism of unpredictable ELS‐induced increase in colonic permeability differs from the mechanism described by Zheng et al where CORT‐induced activation of GR on colonic epithelial cells caused a decrease in tight junction proteins in colonic epithelial cells and an increase in colonic permeability 43 . We previously showed that activation of the CeA, with stereotaxically placed CORT pellets, induced colonic hyperpermeability 44 . Like the OAL model, stereotaxic placement of CORT pellets on the CeA does not affect circulating CORT levels 45 .…”

“…43 We previously showed that activation of the CeA, with stereotaxically placed CORT pellets, induced colonic hyperpermeability. 44 Like the OAL model, stereotaxic placement of CORT pellets on the CeA does not affect circulating CORT levels. 45 Therefore, it is plausible that a hyperactive amygdala might contribute to abnormal colonic permeability.…”