Chronic Stress Modulates the Mucin Components of the Intestinal Barrier and the Intestinal Morphology

Abstract

Objectives: The aim for this study was to investigate the effects of chronic restraint stress on the expression of mucins that comprises the integral component of the gastrointestinal barrier. Design and Methods: A completely randomized design was used for the study. Sixteen ICR male mice were randomly divided into treated and control animals. Restraint stress was applied to the treated mice for 21 days. Body weight and feed consumed were regularly recorded. After 21 days mice were euthanized and blood and gastrointestinal tissues were collected. Serum corticosterone levels were determined. Intestinal sections were fixed, paraffin-embedded, sectioned, stained with alcian-blue-periodic acid Schiff stain to visualize goblet cells. Expression of mucosa mucins was determined using qPCR and western blotting. Results: As expected stressed mice showed higher corticosterone levels than the control mice (5082±1975 vs 1566±1236 pg/ml, P = 0.002). At the end of the study the body weight was lower in the stressed group (32±2 vs 36.0±3 g) even though the cumulative food consumed in both groups was not different. Stressed mice had lower goblet cell count in the duodenum, jejunum, ileum and colon (8±2, 7±1, 9±1, and 25±8 vs 14±1, 14±1, 11±2 and 40±9, respectively), and shorter villi in the duodenum and jejunum (316±82 and 256±73 vs 440±73 and 357±35 µm, respectively). Expressions of mRNA for Muc1 and Muc4 in the colon of stressed animals were upregulated (1.5 and 2.2 fold increase, and P values of 0.05 and 0.01, respectively). This mRNA upregulation was accompanied by increased expression of Muc1 and 4 proteins in the colon. Conclusion: These findings suggest that chronic stress affects the intestinal barrier by reducing the number of the mucin-producing goblet cells, shortening the villi and upregulating Muc1 and Muc4 in the colon.