Effects of chronic unpredictable stress on intestinal morphology in Wistar rats

Year 2019, Volume: 13 Issue: 1, 27 - 32, 29.04.2019

Ufuk Çorumlu Osman Özcan Aydın Emel Ulupınar

Abstract

Objectives: Stressful events might cause immune dysfunction and trigger various disorders. Adverse effects of acute or
chronic stress exposure on the gastrointestinal system have been shown previously in several studies. In this experimental
study, we used chronic unpredictable stress (CUS) paradigm to better mimic effects of the intermittent exposure to daily life
stress and investigated the morphometric alterations occurring in the small intestines of rats.

Methods: Male Wistar rats were randomly divided into stress and control groups (n=8, each). While stress group was subjected to chronic unpredictable stress protocol for 21 days, control group remained undisturbed. Intestinal tissue samples
were obtained from two different regions; one was 3-6 cm away from the pylorus and the other one 3-6 cm prior to the
ileocaecal valve. Tissue sections were obtained from paraffin blocks at the thickness of 3 micrometers and stained with
hematoxylin-eosin (HE) or periodic acid-Shiff (PAS). The lengths of villi were measured from the basal membrane to the top
of the villus. The ratio of degranulating and non-degranulating mast cells per unit area were estimated by point counting
method.

Results: The mean villi length in the stress group were significantly higher (p<0.01) than those of the control group.
Degranulation to non-degranulation ratio of the mast cells were 40% and 54% in the control and stress groups, respectively.

Conclusion: Animals exposed to chronic unpredictable stress protocol displayed a significant elongation in the villi of small
intestines and an increase in the number of degranulating mast cells in the intestinal mucosa. Since activation of mast cells
causes releasing of various chemical mediators and growth factors, it is plausible that stressed animals developed an adaptation mechanism to enhance the capacity for absorption and digestion per unit length of the guts. 

Keywords

chronic unpredictable stress; gastrointestinal system; mast cell; villus length

References

• 1. Söderholm JD, Yang PC, Ceponis P, Vohra A, Riddell R, Sherman PM, Perdue MH. Chronic stress induces mast cell-dependent bacterial adherence and initiates mucosal inflammation in rat intestine. Gastroenterology 2002;123:1099–108. 2. Santos J, Benjamin M, Yang PC, Prior T, Perdue MH. Chronic stress impairs rat growth and jejunal epithelial barrier function: role of mast cells. Am J Physiol Gastrointest Liver Physiol 2000;278: G847–54. 3. Tache Y, Martinez V, Wang L, Million M. CRF1 receptor signaling pathways are involved in stress-related alterations of colonic function and viscerosensitivity: implications for irritable bowel syndrome. Br J Pharmacol 2004;141:1321–30. 4. Vicario M, Guilarte M, Alonso C, Yang P, Martínez C, Ramos L, Lobo B, González A, Guilà M, Pigrau M, Saperas E, Azpiroz F, Santos J. Chronological assessment of mast cell-mediated gut dysfunction and mucosal inflammation in a rat model of chronic psychosocial stress. Brain Behav Immun 2010;24:1166–75. 5. Larsen MH, Mikkelsen JD, Hay-Schmidt A, Sandi C. Regulation of brain-derived neurotrophic factor (BDNF) in the chronic unpredictable stress rat model and the effects of chronic antidepressant treatment. J Psychiatr Res 2010;44:808–16. 6. Willner P. Validity, reliability and utility of the chronic mild stress model of depression: a 10-year review and evaluation. Psychopharmacology (Berl) 1997;134:319–29. 7. Groot Kormelink T, Arkesteijn GJ, van de Lest CH, Geerts WJ, Goerdayal SS, Altelaar MA, Redegeld FA, Nolte-’t Hoen EN, Wauben MH. Mast cell degranulation is accompanied by the release of a selective subset of extracellular vesicles that contain mast cellspecific proteases. J Immunol Epub 2016;197:3382–92. 8. Bradding P, Holgate ST. Immunopathology and human mast cell cytokines. Crit Rev Oncol Hematol 1999;31:119–33. 9. Galli SJ, Kalesnikoff J, Grimbaldeston MA, Piliponsky AM, Williams CM, Tsai M. Mast cells as “tunable” effector and immunoregulatory cells: recent advances. Annu Rev Immunol 2005;23:749–86. 10. Yang PC, Jury J, Söderholm JD, Sherman PM, McKay DM, Perdue MH. Chronic psychological stress in rats induces intestinal sensitization to luminal antigens. Am J Pathol 2006;168:104–14. 11. Wilson LM, Baldwin AL. Environmental stress causes mast cell degranulation, endothelial and epithelial changes, and edema in the rat intestinal mucosa. Microcirculation 1999;6:189–98. 12. Santos J, Yang PC, Söderholm JD, Benjamin M, Perdue MH. Role of mast cells in chronic stress induced colonic epithelial barrier dysfunction in the rat. Gut 2001;48:630–6.13. Santos J, Guilarte M, Alonso C, Malagelada JR. Pathogenesis of irritable bowel syndrome: the mast cell connection. Scand J Gastroenterol 2005;40:129–40. 14. Barreau F, Ferrier L, Fioramonti J, Bueno L. New insights in the etiology and pathophysiology of irritable bowel syndrome: contribution of neonatal stress models. Pediatr Res 2007;62:240– 5. 15. Söderholm JD, Perdue MH. Stress and gastrointestinal tract. II. Stress and intestinal barrier function. Am J Physiol Gastrointest Liver Physiol 2001;280:G7–13. 16. Skaper SD, Giusti P, Facci L. Microglia and mast cells: two tracks on the road to neuroinflammation. FASEB J 2012;26:3103–17. 17. Afrin LB, Khoruts A. Mast cell activation disease and microbiotic interactions. Clin Ther 2015;37:941–53. 18. Barbara G, Stanghellini V, De Giorgio R, Corinaldesi R. Functional gastrointestinal disorders and mast cells: implications for therapy. Neurogastroenterol Motil 2006;18:6–17. 19. Yu LC, Perdue MH. Role of mast cells in intestinal mucosal function: studies in models of hypersensitivity and stress. Immunol Rev 2001;179:61–73.