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Can Sertraline and Nortriptyline Protect the Neurons in Submucosal and Myenteric Plexuses of Rat’s Colon Against Stress?

  • Ali Noorafshan
  • Majid Yousefi
  • Leila Hosseini
  • Saied Karbalay-DoustEmail author
Original Article
  • 28 Downloads

Abstract

Background

The colon is partly controlled by myenteric and submucosal plexuses, which respond to stress and lead to some gastrointestinal disorders. These plexuses play roles in irritable bowel syndrome. Patients suffering from this syndrome can be treated with some antidepressants, including sertraline and nortriptyline.

Aims

The primary aim of study was to compare the effect of a sertraline and a nortriptyline on the structural changes of the enteric neurons after stress exposure in both sexes. The secondary objectives were to evaluate the effects of stress on the submucosal and myenteric plexuses.

Methods

Male and female Sprague-Dawley rats were assigned to four subgroups. The first subgroup received no stress. The other three subgroups received chronic variable stress (CVS) and were given phosphate buffer, sertraline (10 mg/kg/day), or nortriptyline (10 mg/kg/day). After 45 days, the neuron number in their colon plexuses was estimated using the stereologic method.

Results

The number of neurons increased by 40–51% in the submucosal plexus and by 57–69% in the myenteric plexus in the CVS group compared with the control group (p < 0.002) without any sex preference. The increment was significantly higher in the myenteric plexus than in the submucosal plexus (p < 0.05). Moreover, co-treatment of stressed rats with sertraline and nortriptyline could prevent the cellular hyperplasia of the plexuses, with more effective action for sertraline (p < 0.02).

Conclusions

Stress exposure for 45 days induced hyperplasia of the colon’s enteric plexuses in both sexes. However, these drugs could prevent the changes, with a more effective action for sertraline.

Keywords

Stress Enteric plexus Colon Sertraline Nortriptyline Rat 

Notes

Acknowledgments

This work was performed at the Histomorphometry and Stereology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran. This study was a part of the thesis written by Majid Yousefi and financially supported by the Research Vice-chancellor of Shiraz University of Medical Sciences (approval no. 95-01-01-12986). The authors thank Ms. A. Keivanshekouh at the Research Improvement Center of Shiraz University of Medical Sciences for improving the English in the manuscript and express their appreciation to Rouz Darou Pharmaceutical Co. for their kind provision of sertraline.

Author's contribution

AN designed the study. LH researched and discussed the physiopathology of the syndrome and medication dosage. MY carried out the animal experiments. SK collected the data. AN, LH, and SK drafted and revised the whole manuscript.

Compliance with ethical standards

Conflict of interest

The authors declare no conflict of interests.

Ethical approval

The animal experiments were approved by the Ethics Committee of Shiraz University of Medical Sciences, Shiraz, Iran (approval no. 95-01-01-12986).

References

  1. 1.
    Konturek PC, Brzozowski T, Konturek SJ. Stress and the gut: pathophysiology, clinical consequences, diagnostic approach and treatment options. J Physiol Pharmacol. 2011;62:591–599.Google Scholar
  2. 2.
    Saunders PR, Kosecka U, McKay DM, et al. Acute stressors stimulate ion secretion and increase epithelial permeability in rat intestine. Am J Physiol. 1994;267:G794–G799.Google Scholar
  3. 3.
    Li S, Fei G, Fang X, et al. Changes in enteric neurons of small intestine in a rat model of irritable bowel syndrome with diarrhea. J Neurogastroenterol Motil. 2016;22:310–320.  https://doi.org/10.5056/jnm15082.CrossRefGoogle Scholar
  4. 4.
    Zhao Y, Qian L. Homocysteine-mediated intestinal epithelial barrier dysfunction in the rat model of irritable bowel syndrome caused by maternal separation. Acta Biochim Biophys Sin (Shanghai). 2014;46:917–919.  https://doi.org/10.1093/abbs/gmu076.CrossRefGoogle Scholar
  5. 5.
    Hungin AP, Becher A, Cayley B, et al. Irritable bowel syndrome: an integrated explanatory model for clinical practice. Neurogastroenterol Motil. 2015;27:750–763.  https://doi.org/10.1111/nmo.12524.CrossRefGoogle Scholar
  6. 6.
    Usai-Satta P, Bellini M, Lai M, Oppia F, et al. Therapeutic approach for irritable bowel syndrome: old and new strategies. Curr Clin Pharmacol. 2018;.  https://doi.org/10.2174/1574884713666180807143606.Google Scholar
  7. 7.
    Siafis S, Papazisis G. Detecting a potential safety signal of antidepressants and type 2 diabetes: a pharmacovigilance-pharmacodynamic study. Br J Clin Pharmacol. 2018;84:2405–2414.  https://doi.org/10.1111/bcp.13699.CrossRefGoogle Scholar
  8. 8.
    Rho S-G, Kim YS, Choi SC, et al. Sweet food improves chronic stress-induced irritable bowel syndrome-like symptoms in rats. World J Gastroenterol. 2014;20:2365–2373.  https://doi.org/10.3748/wjg.v20.i9.2365.CrossRefGoogle Scholar
  9. 9.
    Kim YS, Lee MY, Choi CS, Sohn YW, et al. The effect of chronic variable stress on bowel habit and adrenal function in rats. J Gastroenterol Hepatol. 2008;23:1840–1846.  https://doi.org/10.1111/j.1440-1746.2008.05524.x.CrossRefGoogle Scholar
  10. 10.
    Hyde DM, Tyler NK, Plopper CG. Morphometry of the respiratory tract: avoiding the sampling, size, orientation, and reference traps. Toxicol Pathol. 2007;35:41–48.CrossRefGoogle Scholar
  11. 11.
    Noorafshan A, Abdollahifar MA, Karbalay-Doust S, et al. Sertraline and curcumin prevent stress-induced morphological changes of dendrites and neurons in the medial prefrontal cortex of rats. Folia Neuropathol. 2015;53:69–79.CrossRefGoogle Scholar
  12. 12.
    Bae SK, Yang KH, Aryal DK, et al. Pharmacokinetics of amitriptyline and one of its metabolites, nortriptyline, in rats: little contribution of considerable hepatic first-pass effect to low bioavailability of amitriptyline due to great intestinal first-pass effect. J Pharm Sci. 2009;98:1587–1601.  https://doi.org/10.1002/jps.21511.CrossRefGoogle Scholar
  13. 13.
    Tagliari B, dos Santos TM, Cunha AA, et al. Chronic variable stress induces oxidative stress and decreases butyrylcholinesterase activity in blood of rats. J Neural Transm (Vienna). 2010;117:1067–1076.  https://doi.org/10.1007/s00702-010-0445-0.CrossRefGoogle Scholar
  14. 14.
    Clouse RE. Antidepressants for irritable bowel syndrome. Gut. 2003;52:598–599.CrossRefGoogle Scholar
  15. 15.
    Noorafshan A, Hoseini L, Karbalay-Doust S, et al. A simple stereological method for estimating the number and the volume of the pancreatic beta cells. JOP. 2012;13:427–432.  https://doi.org/10.6092/1590-8577/802.Google Scholar
  16. 16.
    Nyengaard JR, Alwasel SH. Practical stereology of the stomach and intestine. Ann Anat. 2014;196:41–47.  https://doi.org/10.1016/j.aanat.2013.10.007.CrossRefGoogle Scholar
  17. 17.
    Hansen CF, Vassiliadis E, Vrang N, et al. The effect of ileal interposition surgery on enteroendocrine cell numbers in the UC Davis type 2 diabetes mellitus rat. Regul Pept. 2014;189:31–39.  https://doi.org/10.1016/j.regpep.2014.01.002.CrossRefGoogle Scholar
  18. 18.
    Gareau MG, Jury J, Perdue MH. Neonatal maternal separation of rat pups results in abnormal cholinergic regulation of epithelial permeability. Am J Physiol Gastrointest Liver Physiol. 2007;293:G198–G203.CrossRefGoogle Scholar
  19. 19.
    Medland JE, Pohl CS, Edwards LL, et al. Early life adversity in piglets induces long-term upregulation of the enteric cholinergic nervous system and heightened, sex-specific secretomotor neuron responses. Neurogastroenterol Motil. 2016;28:1317–1329.  https://doi.org/10.1111/nmo.12828.CrossRefGoogle Scholar
  20. 20.
    Million M, Larauche M. Stress, sex, and the enteric nervous system. Neurogastroenterol Motil. 2016;28:1283–1289.  https://doi.org/10.1111/nmo.12937.CrossRefGoogle Scholar
  21. 21.
    Taché Y, Million M. Role of corticotropin-releasing factor signaling in stress-related alterations of colonic motility and hyperalgesia. J Neurogastroenterol Motil. 2015;21:8–24.  https://doi.org/10.5056/jnm14162.CrossRefGoogle Scholar
  22. 22.
    Petersén A, Wörtwein G, Gruber SH, et al. Nortriptyline mediates behavioral effects without affecting hippocampal cytogenesis in a genetic rat depression model. Neurosci Lett. 2009;451:148–151.  https://doi.org/10.1016/j.neulet.2008.12.046.CrossRefGoogle Scholar
  23. 23.
    Chen L, Ilham SJ, Feng B. Pharmacological approach for managing pain in irritable bowel syndrome: a review article. Anesth Pain Med. 2017;7:e42747.  https://doi.org/10.5812/aapm.42747. (eCollection 2017 Apr. Review).CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Histomorphometry and Stereology Research CenterShiraz University of Medical SciencesShirazIran
  2. 2.Anatomy Department, School of MedicineShiraz University of Medical SciencesShirazIran
  3. 3.Department of Traditional Medicine, School of MedicineShiraz University of Medical SciencesShirazIran

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