Abstract

BackgroundDuring weaning, babies and young animal often experience diarrhea from food intolerance and/or decreasing levels of maternal antibodies, and diarrhea tends to be particularly severe during the early-weaned period, which often exhibits an underdeveloped immune system, a disturbed gut environment and results in nutrient malabsorption and dehydration. It was deduced that neuroendocrine might have close relation with diarrhea, especially 5-HT.MethodsTo explore the role of serotonin (5-HT) in weaning mice subjected to stress-induced diarrhea, 21-day-old weaned mice were divided into the following groups: control group, stress-induced diarrhea group (restrained by binding the hind limbs and intragastric administration of folium sennae with 0.4 g/mL, 15 mL/kg body weight) and para-chlorophenylalanine (PCPA) + stress-induced diarrhea group (30 mg/mL, 300 mg/kg body weight PCPA intraperitoneal injection before stress-induced diarrhea treatment).ResultsBased on results from enzyme-linked immunosorbent assays, histological staining, lymphocyte proliferation assays and flow cytometry analysis, we found that the mice experienced increases in several stress markers, which coincided with severe diarrhea and an increase in 5-HT levels. However, pre-treatment with PCPA resulted in a decrease in the stress indicators and the severity of diarrhea, which correlated with decreased 5-HT levels. Interestingly, stress-induced diarrhea caused changes in various aspects of the immune system, including the amount of intraepithelium lymphocytes, CD4+/CD8+ T lymphocyte populations, B and T lymphocyte proliferation, and the secretion of sIgA and cytokines in the small intestine and ileum. However, these immune system changes could be reversed upon treatment with PCPA.ConclusionsWe observed a distinct correlation between 5-HT levels and the occurrence of stress-induced diarrhea in weaning mice, which may result in the deregulation of the mucosal immune system.

Highlights

  • During weaning, babies and young animal often experience diarrhea from food intolerance and/or decreasing levels of maternal antibodies, and diarrhea tends to be severe during the early-weaned period, which often exhibits an underdeveloped immune system, a disturbed gut environment and results in nutrient malabsorption and dehydration

  • Stress-induced diarrhea coincided with increased indicators of stress activity in the mice, which could be partially reversed upon pre-treatment with PCPA

  • The IL-4 and IL–10 concentrations decreased in the colon and ileum in the stress-induced diarrhea group but increased in the jejunum of these mice. These results suggest that stress-induced diarrhea caused most of the inflammation associated with the small intestine and the colon. 5-HT levels increased in the stress-induced diarrhea group, which correlated with cytokine levels

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Summary

Introduction

Babies and young animal often experience diarrhea from food intolerance and/or decreasing levels of maternal antibodies, and diarrhea tends to be severe during the early-weaned period, which often exhibits an underdeveloped immune system, a disturbed gut environment and results in nutrient malabsorption and dehydration. Babies often experience diarrhea from food intolerance and/or decreasing levels of maternal antibodies [2]. Porcine GI mucosa predominantly expresses the 5-HT4 receptor splice variant, suggesting that this receptor plays a large role in 5-HT-mediated mucosal effects [15]. Many 5-HT immunoreactive cells are in contact with or are in very close proximity to CD3+ and CD20+ lymphocytes within the epithelium of the intestines of rhesus monkeys (Macaca mulatta), which further supports a possible role for 5-HT in the gut mucosal immune response [17]. Antagonism of the 5-HT1B receptor inhibits the proliferation of both human and murine primary helper T cells as well as the proliferation of human helper T cell lines [18]

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