Effects of fluoxetine on mast cell morphology and protease-1 expression in gastric antrum in a rat model of depression

World J Gastroenterol. 2008 Dec 7;14(45):6993-8. doi: 10.3748/wjg.14.6993.

Abstract

Aim: To investigate the effects of fluoxetine on depression-induced changes of mast cell morphology and protease-1 (rMCP-1) expression in rats.

Methods: A Sprague-Dawley rat model of chronic stress-induced depression was established. Fifty experimental rats were randomly divided into the following groups: normal control group, fluoxetine+normal control group, depressed model group, saline+depressed model group, and fluoxetine+depressed model group. Laser scanning confocal microscopy (LSCM) immunofluorecence and RT-PCR techniques were used to investigate rMCP-1 expression in gastric antrum. Mast cell morphology was observed under transmission electron microscopy. ANOVA was used for statistical analysis among groups.

Results: Morphologic observation indicated that depression induced mast cell proliferation, activation, and granule hyperplasia. Compared with the normal control group, the average immunofluorescence intensity of gastric antrum rMCP-1 significantly increased in depressed model group (37.4+/-7.7 vs 24.5+/-5.6, P<0.01) or saline+depressed model group (39.9+/-5.0 vs 24.5+/-5.6, P<0.01), while there was no significant difference between fluoxetine + normal control group (23.1+/-3.4) or fluoxetine+depressed model group (26.1+/-3.6) and normal control group. The average level of rMCP-1mRNA of gastric antrum significantly increased in depressed model group (0.759+/-0.357 vs 0.476+/-0.029, P<0.01) or saline+depressed model group (0.781+/-0.451 vs 0.476+/-0.029, P<0.01), while no significant difference was found between fluoxetine+normal control group (0.460+/-0.027) or fluoxetine+depressed model group (0.488+/-0.030) and normal control group. Fluoxetine showed partial inhibitive effects on mast cell ultrastructural alterations and de-regulated rMCP-1 expression in gastric antrum of the depressed rat model.

Conclusion: Chronic stress can induce mast cell proliferation, activation, and granule hyperplasia in gastric antrum. Fluoxetine counteracts such changes in the depressed rat model.

MeSH terms

  • Animals
  • Cell Proliferation / drug effects
  • Chemokine CCL2 / drug effects
  • Chemokine CCL2 / genetics
  • Chemokine CCL2 / metabolism*
  • Depression / drug therapy
  • Depression / metabolism*
  • Depression / pathology*
  • Disease Models, Animal
  • Fluoxetine / pharmacology*
  • Fluoxetine / therapeutic use
  • Hyperplasia / metabolism
  • Hyperplasia / pathology
  • Male
  • Mast Cells / drug effects
  • Mast Cells / pathology*
  • Pyloric Antrum / drug effects
  • Pyloric Antrum / metabolism*
  • Pyloric Antrum / pathology*
  • RNA, Messenger / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Selective Serotonin Reuptake Inhibitors / pharmacology
  • Selective Serotonin Reuptake Inhibitors / therapeutic use
  • Stress, Psychological / metabolism
  • Stress, Psychological / pathology

Substances

  • Ccl2 protein, rat
  • Chemokine CCL2
  • RNA, Messenger
  • Serotonin Uptake Inhibitors
  • Fluoxetine