Explore the vast range of titles available.

Early-life stress is a main contributory factor to the onset of depression. Treatments remain inadequate and as such, a large unmet medical need for novel therapeutics remains. Impeding advancement is the poor understanding of the molecular pathology. microRNAs (miRNAs) are novel regulators of gene expression. A paucity of information regarding their role in depressive pathology and antidepressant action remains. This study investigated changes to hippocampal miRNA levels induced via early-life stress in Sprague–Dawley rats and whether antidepressant treatments could reverse these changes. Investigated were the selective serotonin reuptake inhibitor fluoxetine, the rapid acting N-methyl-d-aspartate receptor antagonist ketamine and electroconvulsive shock therapy (ECT). Microarray analysis revealed early-life stress affected the expression of multiple hippocampal miRNAs. Antidepressant treatments reversed some of these effects including a stress-induced change to miR-451. Ketamine and ECT possessed the highest number of common targets suggesting convergence on common pathways. Interestingly all three treatments possessed miR-598-5p as a common target. This demonstrates that changes to hippocampal miRNA expression may represent an important component of stress-induced pathology and antidepressant action may reverse these.

The interface between psychiatry and stress-related gastrointestinal disorders (GI), such as irritable bowel syndrome (IBS), is well established, with anxiety and depression the most frequently occurring comorbid conditions. Moreover, stress-sensitive Wistar Kyoto (WKY) rats, which display anxiety- and depressive-like behaviors, exhibit GI disturbances akin to those observed in stress-related GI disorders. Additionally, there is mounting preclinical and clinical evidence implicating mast cells as significant contributors to the development of abdominal visceral pain in IBS. In this study we examined the effects of the rat connective tissue mast cell (CTMC) stabiliser, disodium cromoglycate (DSCG) on visceral hypersensitivity and colonic ion transport, and examined both colonic and peritoneal mast cells from stress-sensitive WKY rats. DSCG significantly decreased abdominal pain behaviors induced by colorectal distension in WKY animals independent of a reduction in colonic rat mast cell mediator release. We further demonstrated that mast cell-stimulated colonic ion transport was sensitive to inhibition by the mast cell stabiliser DSCG, an effect only observed in stress-sensitive rats. Moreover, CTMC-like mast cells were significantly increased in the colonic submucosa of WKY animals, and we observed a significant increase in the proportion of intermediate, or immature, peritoneal mast cells relative to control animals. Collectively our data further support a role for mast cells in the pathogenesis of stress-related GI disorders.

The interface between psychiatry and stress-related gastrointestinal disorders (GI), such as irritable bowel syndrome (IBS), is well established, with anxiety and depression the most frequently occurring comorbid conditions. Moreover, stress-sensitive Wistar Kyoto (WKY) rats, which display anxiety- and depressive-like behaviors, exhibit GI disturbances akin to those observed in stress-related GI disorders. Additionally, there is mounting preclinical and clinical evidence implicating mast cells as significant contributors to the development of abdominal visceral pain in IBS. In this study we examined the effects of the rat connective tissue mast cell (CTMC) stabiliser, disodium cromoglycate (DSCG) on visceral hypersensitivity and colonic ion transport, and examined both colonic and peritoneal mast cells from stress-sensitive WKY rats. DSCG significantly decreased abdominal pain behaviors induced by colorectal distension in WKY animals independent of a reduction in colonic rat mast cell mediator release. We further demonstrated that mast cell-stimulated colonic ion transport was sensitive to inhibition by the mast cell stabiliser DSCG, an effect only observed in stress-sensitive rats. Moreover, CTMC-like mast cells were significantly increased in the colonic submucosa of WKY animals, and we observed a significant increase in the proportion of intermediate, or immature, peritoneal mast cells relative to control animals. Collectively our data further support a role for mast cells in the pathogenesis of stress-related GI disorders.