Dataset Information

Depressive disorder and gastrointestinal dysfunction after myocardial infarct are associated with abnormal tryptophan-5-hydroxytryptamine metabolism in rats.

ABSTRACT: In this study, we investigated the relationship between tryptophan-5-hydroxytryptamine metabolism, depressive disorder, and gastrointestinal dysfunction in rats after myocardial infarction. Our goal was to elucidate the physiopathologic bases of somatic/psychiatric depression symptoms after myocardial infarction. A myocardial infarction model was established by permanent occlusion of the left anterior descending coronary artery. Depression-like behavior was evaluated using the sucrose preference test, open field test, and forced swim test. Gastric retention and intestinal transit were detected using the carbon powder labeling method. Immunohistochemical staining was used to detect indoleamine 2,3-dioxygenase expression in the hippocampus and ileum. High-performance liquid chromatography with fluorescence and ultraviolet detection determined the levels of 5-hydroxytryptamine, its precursor tryptophan, and its metabolite 5-hydroxyindoleacetic acid in the hippocampus, distal ileum, and peripheral blood. All data were analyzed using one-way analyses of variance. Three weeks after arterial occlusion, rats in the model group began to exhibit depression-like symptoms. For example, the rate of sucrose consumption was reduced, the total and central distance traveled in the open field test were reduced, and immobility time was increased, while swimming, struggling and latency to immobility were decreased in the forced swim test. Moreover, the gastric retention rate and gastrointestinal transit rate were increased in the model group. Expression of indoleamine 2,3-dioxygenase was increased in the hippocampus and ileum, whereas 5-hydroxytryptamine metabolism was decreased, resulting in lower 5-hydroxytryptamine and 5-hydroxyindoleacetic acid levels in the hippocampus and higher levels in the ileum. Depressive disorder and gastrointestinal dysfunction after myocardial infarction involve abnormal tryptophan-5-hydroxytryptamine metabolism, which may explain the somatic, cognitive, and psychiatric symptoms of depression commonly observed after myocardial infarction. Peripheral 5-hydroxytryptamine is an important substance in the gut-brain axis, and its abnormal metabolism is a critical finding after myocardial infarct.

SUBMITTER: Lu X

PROVIDER: S-EPMC5315315 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Depressive disorder and gastrointestinal dysfunction after myocardial infarct are associated with abnormal tryptophan-5-hydroxytryptamine metabolism in rats.

Lu Xiaofang X Wang Yuefen Y Liu Chunyan C Wang Yangang Y

PloS one 20170217 2

In this study, we investigated the relationship between tryptophan-5-hydroxytryptamine metabolism, depressive disorder, and gastrointestinal dysfunction in rats after myocardial infarction. Our goal was to elucidate the physiopathologic bases of somatic/psychiatric depression symptoms after myocardial infarction. A myocardial infarction model was established by permanent occlusion of the left anterior descending coronary artery. Depression-like behavior was evaluated using the sucrose preference ...[more]

PMID: 28212441

Similar Datasets

Project description:Background: Major depressive disorder (MDD) is an affective disorder that is harmful to both physical and mental health. Abnormal self-knowledge, which refers to abnormal judgments about oneself, is a core symptom of depression. However, little research has summarized how and why patients with MDD differ from healthy individuals in terms of self-knowledge. Objective: To gain a better understanding of MDD, we reviewed previous studies that focused on the behavioral and neurological changes of self-knowledge in this illness. Main Findings: On the behavioral level, depressed individuals exhibited negative self-knowledge in an explicit way, while more heterogeneous patterns were reported in implicit results. On the neurological level, depressed individuals, as compared with non-depressed controls, showed abnormal self-referential processing in both early perception and higher cognitive processing phases during the Self-Referential Encoding Task. Furthermore, fMRI studies have reported aberrant activity in the medial prefrontal cortex area for negative self-related items in depression. These results revealed several behavioral features and brain mechanisms underlying abnormal self-knowledge in depression. Future Studies: The neural mechanism of implicit self-knowledge in MDD remains unclear. Future research should examine the importance of others' attitudes on the self-concept of individuals with MDD, and whether abnormal self-views may be modified through cognitive or pharmacological approaches. In addition, differences in abnormal self-knowledge due to genetic variation between depressed and non-depressed populations remain unconfirmed. Importantly, it remains unknown whether abnormal self-knowledge could be used as a specific marker to distinguish healthy individuals from those with MDD. Conclusion: This review extends our understanding of the relationship between self-knowledge and depression by indicating several abnormalities among individuals with MDD and those who are at risk for this illness.

Project description:Background: Major Depressive Disorder (MDD) is a moderately heritable disorder with a high lifetime prevalence. At present, laboratory blood tests to support MDD diagnosis are not available. Methods: We used a classifier approach on blood gene expression profiles of a unique set of non-medicated subjects (MDD patients and controls) to select genes of which expression is predictive for disease status. To reveal blood gene expression changes related to MDD disease, we applied a powerful ex vivo stimulus to the blood, i.e. incubation with lipopolysaccharide (LPS; 10 ng/ml blood). Results: Based on LPS-stimulated blood gene expression using whole-genome microarrays in 42 subjects (primary cohort; 21 MDD patients (mean age 42.3 years), 21 healthy controls (mean age 41.9 years)), we identified a set of genes (CAPRIN1, CLEC4A, KRT23, MLC1, PLSCR1, PROK2, ZBTB16) that serves as a molecular signature of MDD. These findings were validated for the primary cohort using an independent quantitative PCR method (P = 0.007). The difference between depressive patients and controls was confirmed (P = 0.019) in a replication cohort of 13 patients with MDD (mean age 42.8 years) and 14 controls (mean age 45.6 years). The MDD-signature score comprised of expression levels of 7 genes could discriminate depressive patients from controls with sensitivity of 76.9% and specificity of 71.8%. Conclusions: We show for the first time that molecular analysis of stimulated blood cells can be used as an endophenotype for MDD diagnosis, which is a milestone in establishing biomarkers for neuropsychiatric disorders with moderate heritability in general. Our results may provide a new entry point for following and predicting treatment outcome, as well as prediction of severity and recurrence of MDD. In total, 33 MDD patients and 34 healthy controls were analyzed using basal gene expression in whole blood, and gene expression from whole blood that was stimulated with LPS for 5-6 h, using microarrays. Patients were arbitrarily selected from all patients to serve as primary cohort (nMDD = 21 (MDD01-MDD21); nControls = 21 (Con01-Con21)), or replication cohort (nMDD = 12 (MDD22-MDD35); nControls = 13 (Con22-Con37)) using microarrays. This submission does not include Samples CON21_LPS or CON30_LPS.

Project description:BackgroundRecent evidence suggests that antibiotic-induced changes in the composition of intestinal microflora, as well as the systemic immunoendocrine effects that result from them, can modulate myocardial tolerance to ischemia-reperfusion injury. The aim of this study was to investigate the effects of tetracycline (TTC) on myocardial infarct size in the isolated hearts obtained from obese rats with chemically-induced colitis (CIC). The association between TTC-induced changes in infarct size and intestinal microbiome composition as well as plasma levels of cytokines and short-chain fatty acids (SCFAs) was also studied.MethodsObesity was induced in Wistar rats by feeding them a high-fat, high-carbohydrate diet for five weeks. A single rectal administration of 3% acetic acid (2 mL) to the rats resulted in CIC. Healthy rats as well as obese rats with CIC received TTC (15 mg daily for 3 days) via gavage. The rats were euthanized, after which isolated heart perfusion with simulated global ischemia and reperfusion was performed. Infarct size was determined histochemically. Lipopolysaccharide (LPS) and cytokine levels in plasma were measured by enzyme-linked immunosorbent assay, whereas SCFA levels in plasma were measured by gas chromatography/mass spectrometry. The intestinal microbiome was analyzed using reverse transcription polymerase chain reaction.ResultsThe treatment with TTC resulted in significant infarct size limitation (50 ± 7 vs. 62 ± 4% for the control mice, p < 0.05) in the hearts from intact animals. However, infarct size was not different between the control rats and the obese rats with CIC. Furthermore, infarct size was significantly larger in TTC-treated obese rats with CIC than it was in the control animals (77 ± 5%, p < 0.05). The concentrations of proinflammatory cytokines and LPS in serum were elevated in the obese rats with CIC. Compared to the control rats, the rats with both obesity and CIC had lower counts of Lactobacillus and Bifidobacterium spp. but higher counts of Escherichia coli. The effects of TTC on infarct size were not associated with specific changes in SCFA levels.ConclusionsTTC reduced infarct size in the healthy rats. However, this effect was reversed in the obese animals with CIC. Additionally, it was associated with specific changes in gut microbiota and significantly elevated levels of cytokines and LPS.

Dataset Information

Depressive disorder and gastrointestinal dysfunction after myocardial infarct are associated with abnormal tryptophan-5-hydroxytryptamine metabolism in rats.

Publications

Depressive disorder and gastrointestinal dysfunction after myocardial infarct are associated with abnormal tryptophan-5-hydroxytryptamine metabolism in rats.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets