Protein-caloric restriction induced HPA axis activation and altered the milk composition imprint metabolism of weaned rat offspring.

OBJECTIVES: Maternal protein-caloric restriction during lactation can malprogram offspring into having a lean phenotype associated with metabolic dysfunction in early life and adulthood. The aim of this study was to investigate the relationships between nutritional stress, maternal behavior and metabolism, milk composition, and offspring parameters. Additionally, we focused on the role of hypothalamus-pituitary-adrenal axis hyperactivation during lactation. METHODS: Dams were fed a low-protein diet (4% protein) during the first 2 wk of lactation or a normal-protein diet (20% protein) during all lactation. Analyses of dams, milk, and offspring were conducted on postnatal days (PD) 7, 14, and 21. RESULTS: Body weight and food intake decreased in dams, which was associated with reduced fat pad stores and increased corticosterone levels at PD 14. The stressed low-protein diet dams demonstrated alterations in behavior and offspring care. Despite nutritional deprivation, dams adapted their metabolism to provide adequate energy supply through milk; however, we demonstrated elevated corticosterone and total fat levels in milk at PD 14. Male offspring also showed increased corticosterone at PD 7, associated with a lean phenotype and alterations in white and brown adipose tissue morphology at PD 21. CONCLUSION: Exposure to protein-caloric restriction diet of dams during lactation increased the glucocorticoid levels in dams, milk, and offspring, which is associated with alterations in maternal behavior and milk composition. Thus, glucocorticoids and milk composition may play an important role in metabolic programming induced by maternal undernutrition.

Moderate intestinal immunopathology after acute oral infection with Toxoplasma gondii oocysts is associated with expressive levels of serotonin.

BACKGROUND: Invasion of the intestinal mucosa by T. gondii elicits a local immune response of variable intensity. These reactions can be lethal in C57BL/6 mice. The tissue damage caused by inflammation and the functional effects depend on the host immunity, strain, and developmental form of the parasite. We investigated the effects of acute oral infection with T. gondii on histoarchitecture, enteric nervous system (ENS), and inflammatory markers in the jejunum and ileum of mice. METHODS: Female C57BL/6 mice were divided into a control group and a group orally infected with 1000 sporulated T. gondii oocysts (ME-49 strain). After 5 days, jejunum and ileum were collected and processed for analyzes (e.g., histological and histopathological examinations, ENS, cytokine dosage, myeloperoxidase, nitric oxide activity). MAIN RESULTS: In infected mice, we observed a significant increase in serotonin-immunoreactive cells (5-HT IR) in the intestinal mucosa, as well as cellular infiltrates in the lamina propria, periganglionitis, and ganglionitis in the myenteric plexus. We also noted decreased neuron density in the jejunum, increased population of enteric glial cells in the ileum, histomorphometric changes in the intestinal wall, villi, and epithelial cells, remodeling of collagen fibers, and increased myeloperoxidase activity, cytokines, and nitric oxide in the intestine. CONCLUSIONS AND INFERENCES: Acute infection of female mice with T. gondii oocysts resulted in changes in ENS and a marked increase in 5-HT. These changes are consistent with its modulatory role in the development of moderate acute inflammation. The use of this experimental model may lend itself to studies aimed at understanding the pathophysiological mechanisms of intestinal inflammation in humans involving ENS.

Acute infection with Toxoplasma gondii oocysts preferentially activates non-neuronal cells expressing serotonin in the jejunum of rats.

The interaction of Toxoplasma gondii with the gastrointestinal tract of its host is highly regulated. Once ingested, the parasite crosses the epithelium without altering the permeability of the intestinal barrier. Nevertheless, many studies report alterations ranging from structural to functional damage in cells and tissues that make up the wall of the small and large intestine. Although the immune response to the parasite has been extensively studied, the role of serotonin (5-HT) in toxoplasmosis is poorly understood. Here we investigate the distribution of cells expressing 5-HT and its effects on cells and tissues of the jejunal wall of rats after 2, 3, or 7 days of T. gondii infection. KEY RESULTS: Our results show that transposition of the jejunal epithelium by T. gondii leads to ruptures in the basement membrane and activation of the immune system, as confirmed by the decrease in laminin immunostaining and the increase in the number of mast cells, respectively. CONCLUSIONS AND INFERENCES: We showed an increase in the number of enterochromaffin cells and mast cells expressing 5-HT in the jejunal wall. We also observed that the percentage of serotonergic mast cells increased in the total population. Thus, we can suggest that oral infection by T. gondii oocysts preferentially activates non-neuronal cells expressing 5-HT. Together, these results may explain both the changes in the extracellular matrix and the morphology of the enteric ganglia.

Toxoplasma gondii causes increased ICAM-1 and serotonin expression in the jejunum of rats 12 h after infection.

OBJECTIVE: To analyze the remodeling dynamics of total collagen, type I and III, the expression of ICAM-1 and 5-HT in the jejunum of rats. METHODS: Twenty-eight Wistar rats were randomly assigned to two experimental groups: the control group (CG, n = 7) and the infected group (receiving 5,000 sporulated T. gondii oocysts - ME49 strain, genotype II, n = 21). Seven infected rats each at 6 (G6), 12 (G12), and 24 (G24) hours post infection were sacrificed and segments of jejunum were collected for standard histological, histochemical, and immunohistochemistry processing techniques. RESULTS: The infection promoted ICAM-1 and 5-HT expression, type III collagen, and total mast cell increases. However, it also caused a reduction in the area occupied by type I collagen fibers, and in submucosa thickness, and caused ganglion and peri-ganglion alterations. CONCLUSION: The structural damage caused by toxoplasmic infection is intense during the first 24 h post inoculation. At peak dissemination, from 12 to 24 h, there is an increase in ICAM-1 and 5-HT expression, with intense migration of mast cells to the site of infection. There was also a reduction in submucosa thickness, and an effective loss of extracellular matrix (ECM) organization, which included changes in the dynamics of type I and III total collagen deposition.