NAD(P) deficiency plays an important role in the restraint-stress-induced depression in the rat model
Ontology highlight
ABSTRACT:
ORGANISM(S): Rattus Norvegicus
TISSUE(S): Urine, Spleen, Brain, Lung, Liver, Kidney, Blood
DISEASE(S): Depression
PROVIDER: ST002298 | MetabolomicsWorkbench |
REPOSITORIES: MetabolomicsWorkbench
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| mwtab | Other |
Items per page: 5 1 - 1 of 1 |
Similar Datasets
Project description:Free Wanderer Powder (FWP) is a classic formula for depression with digestive dysfunctions, i.e., liver-depression and spleen-deficiency syndrome (LDSDS) in Chinese Medicine. But its protective mechanism has not been fully clarified. Here a chronic restraint stress (CRS) induced rat model showed depression with LDSDS in food intake, metabolism, and behaviour tests. Then 75 rats were randomly divided, and received CRS and different treatment with behaviour tests. Expressions of c-Fos and AMPA-type glutamate receptor subunits GluR1-3 in hippocampus CA1, CA3, DG and amygdala BLA were detected by immunohistochemistry, western blot and RT-PCR, respectively. In CRS rats, FWP alleviated depressive behaviour and c-Fos expression. FWP suppressed the increasement of GluR1 in CA1 and DG, p-GluR1 in CA1, and p-GluR2 and GluR3 in BLA. FWP also blocked the decrease of GluR1 and Glur2/3 in CA3, p-GluR1 in CA3, and p-GluR2 in CA1 and CA3. Furthermore, constituents of FWP and their potential targets were explored using UHPLC-MS and systematic bioinformatics analysis. There were 23 constituents identified in FWP, 9 of which regulated glutamatergic synapse. Together, these results suggest that FWP contains effective constituents and alleviates depression with LDSDS by regulating AMPA-type glutamate receptor homeostasis in amygdala and hippocampus.
| S-EPMC7732332 | biostudies-literature
Project description:Depression is a global mental disorder disease and greatly threatened human health and stress is considered to be one of the important factors that lead to depression. In this study, we used newly developed iTRAQ labeling and high performance liquid chromatography (HPLC) and mass spectrum united analysis technology obtained the 2176 accurate proteins. Successively, we used the GO analysis and IPA software to analyze the 98 differentially expressed proteins of liver in depression rats due to chronic restraint stress, showing a map of proteomics analysis of liver proteins from the aspects of related functions, disease and function analysis, canonical pathway analysis, and associated network. This study provide important information for comprehensively understanding the mechanisms of dysfunction or injury in the liver in depression.
| S-EPMC5331273 | biostudies-literature
Project description:Serotonin (5-hydroxytryptamine, 5-HT) dysfunction is associated with the pathophysiology of depression. Tryptophan hydroxylase (TPH), the rate-limiting enzyme in 5-HT biosynthesis, is believed to have essential role in many mental disorders, including depression. In the present study, we generated a rat model of depression by exposing the animals to stress, and the rats were then treated with paroxetine. The results indicated that the concentration of 5-HT in the brain and liver tissues were significantly lower in the rat model of depression than in healthy or treated rats. Immunohistochemical analyses of TPH1/2 showed less TPH1 and TPH2 expression, specifically TPH2, in the brain, liver and kidney of the depressive rats than in the healthy rats; In addition, the two TPH isoforms, TPH1 and TPH2, had different spatial distributions,the mRNAs of the TPH1/2 genes were significantly decreased and TPH1/2 were highly methylated in the depressive model rat, but treatment with paroxetine ameliorated the expression and methylation of TPH1/2. All together, stress was able to inhibit expression of TPH1/2 in brain tissue and decrease concentration of 5-HT, the mechanism maybe involve in increasing the methylation of TPH2 genes promoter; Paroxetine has a role in confronting the effect of stress in depressive rat model.
| S-EPMC5609917 | biostudies-literature
Project description:Background: Clinical findings have shown a negative correlation between the severity of depressive symptoms and serum uric acid levels in men, yet the role of metabolic regulation in the pathophysiology of depression remains largely unknown. Methods: In this study, we utilized an acute restraint-stress-induced male rat model of depression to investigate biochemical changes through NMR-based metabolomics combined with serum biochemical analysis. Additionally, we employed qPCR, immunoblotting, and enzyme activity assays to assess the expression and activity of xanthine oxidoreductase, the rate-limiting enzyme in uric acid production. Results: Our findings indicate the following: (1) restraint stress is a valid method for inducing a depressive phenotype in rats; (2) depressive rats exhibit decreased NAD(P) levels in the liver and increased nicotinamide N-oxide and nicotinate levels in urine, accompanied by decreased levels of uric acid, allantoin, and allantoic acid in serum or tissues; (3) xanthine dehydrogenase activity is diminished in depressive rats without corresponding changes in gene or protein expression. Conclusion: The increased urinary excretion of NAD(P) precursors results in reduced hepatic NAD(P) levels, thereby suppressing NAD-dependent xanthine dehydrogenase activity and diminishing the production of uric acid and its downstream metabolites (allantoin and allantoic acid).
| S-EPMC11676094 | biostudies-literature
Project description:Mammals display wide range of variation in their lifespan. Investigating the molecular networks that distinguish long- from short-lived species has proven useful to identify determinants of longevity. Here, we compared the liver of long-lived naked mole-rats (NMRs) and the phylogenetically closely related, shorter-lived, guinea pigs using an integrated omic approach. We found that NMRs livers display a unique expression pattern of mitochondrial proteins that result in distinct metabolic features of their mitochondria. For instance, we observed a generally reduced respiration rate associated with lower protein levels of respiratory chain components, particularly complex I, and increased capacity to utilize fatty acids. Interestingly, we show that the same molecular networks are affected during aging in both NMR and humans, supporting a direct link to the extraordinary longevity of both species. Finally, we identified a novel longevity pathway and validated it experimentally in the nematode C. elegans.
2018-06-21 | PXD008720 | Pride
Project description:Major depressive disorder is a complex and common mental disease, for which the pathology has not been elucidated. The purpose of this study is to provide knowledge about the importance of mitochondrial dysfunction, dysregulated lipid metabolism and inflammation. Mitochondrial carnitine palmitoyl transferase 1a (CPT1a) is a key molecule involved in lipid metabolism and mutations in CPT1a causing reduced function is hypothesized to have a protective role in the development of depression. Moreover, CPT1a is found to be upregulated in suicide patients with history of depression. Therefore, we hypothesized that inhibition of CPT1a activity can be developed as an innovative treatment strategy for depression. Stress exposure combined with different pharmacological treatment regimens; Etomoxir, CPT1 blocker, and Escitalopram, a favoured antidepressant drug, was applied in state-of-the-art chronic mild stress model. Etomoxir treatment induced statistical significant reduction of anhedonic behavior compared to vehicle treatment (p < 0.0001) and reversed depression-like phenotype in 90% of the rats (p = 0.0007), whereas Escitalopram only proved 57% efficacy. Moreover, Etomoxir revealed downregulation of interferon-γ, interleukin-17α and tumor necrosis factor-α. This indicate that alteration in metabolism is pivotal in the pathogenesis of depression, since CPT1 blockage is highly efficient in treating anhedonia and inflammation, thereby opening up for a novel class of antidepressant medication.
| S-EPMC5438386 | biostudies-literature
Project description:Depression is the second leading cause of disability worldwide. The effects of clinical depression may be mediated by neuroinflammation such as activation of microglia and high levels of proinflammatory cytokines in certain brain areas. Traditional Chinese medicine techniques such as electro-acupuncture (EA) are used extensively in Asia to treat mental health disorders. However, EA has not been rigorously studied in treatment of depression. This study was designed to assess the effectiveness of EA on depressive-like behavior and explore the role of hippocampal neuroinflammation in the potential antidepressant effect of EA. In this study, we used six chronic unpredictable stressors daily in a random sequence for 10 weeks. EA were performed on "Bai-Hui" (Du-20) (+) and "Yang-Ling-Quan" (GB-34, the right side; -) acupoints by an EA apparatus (HANS Electronic Apparatus, LH202H, 2/100 Hz, 0.3 mA) for 30 min once every other day for last 4 weeks. The behavior tests including open field test and forced swimming test, which are widely used to assess depressive and anxiety-like behavior were performed on the Monday and Tuesday of the eleventh week. The results showed that 10 week of chronic unpredictable stress (CUS) caused behavioral deficits in rats and neuroinflammation in hippocampus, such as increased expression of NLRP3 inflammasome components, upregulated mRNA level of IL-1β and the protein level of IL-1β mature form (p17) and activation of microglia. Moreover, 4 weeks of EA treatment significantly attenuated behavioral deficits caused by CUS. EA's antidepressant effect was accompanied by markedly decreased expression of certain NLRP3 inflammasome components and matured IL-1β. Meanwhile, EA treatment can significantly reverse CUS-induced increases in P2X7 receptor, Iba-1, IL-18, TNFα and IL-6 expression and decreases in GFAP expression. In conclusion, EA exhibited the antidepressant effect and alleviated the hippocampal neuroinflammation. These findings may provide insight into the role of hippocampal neuroinflammation in the antidepressant effect of EA.
| S-EPMC6007169 | biostudies-literature
Project description:The naked mole-rat (NMR), Heterocephalus glaber, is a mouse-sized subterranean rodent native to East Africa. Research on NMRs is intensifying in an effort to gain leverage from their unusual physiology, long-life span and cancer resistance for the development of new theraputics. Few studies have attempted to explain the reasons behind the NMR’s cancer resistance, but most prominently Tian et al. reported that NMR cells produce high-molecular weight hyaluronan as a potential cause for the NMR’s cancer resistance. Tian et al. have shown that NMR cells are resistant to transformation by SV40 Large T Antigen (SV40LT) and oncogenic HRAS (HRASG12V), a combination of oncogenes sufficient to transform mouse and rat fibroblasts. We have developed a number of lentiviral vectors to deliver both these oncogenes and generated 106 different cell lines from five different tissues and eleven different NMRs, and report here that contrary to Tian et al.’s observation, NMR cells are susceptible to oncogenic transformation by SV40LT and HRASG12V. Our data thus point to a non-cell autonomous mechanism underlying the remarkable cancer resistance of NMRs. Identifying these non-cell autonomous mechanisms could have significant implications on our understanding of human cancer development.
2020-06-12 | E-MTAB-8932 | biostudies-arrayexpress
Project description:Cognitive flexibility is a higher-order executive function that requires plasticity in neuronal circuits of the prefrontal cortex. Deficits in cognitive flexibility are prominent in a variety of psychiatric disorders, such as major depression, obsessive-compulsive disorder, and posttraumatic stress disorder. Chronic stress induces deficits in cognitive flexibility, perhaps through effects on plasticity, but the mechanism is not well understood. Previous work has demonstrated that stress reduces activity and dendritic elaboration in the medial prefrontal cortex (mPFC). In contrast, stress appears to increase dendritic elaboration in the orbitofrontal cortex (OFC). This suggests that there may be a differential effect of stress on plasticity in different prefrontal cortical areas. To test this hypothesis, we examined the effects of inducing plasticity optogenetically in the OFC on reversal learning, an OFC-mediated form of cognitive flexibility, in stressed and non-stressed rats. Inducing opto-LTD in the projection from mediodorsal thalamus to OFC ameliorated reversal learning deficits in rats exposed to chronic intermittent cold (CIC) stress. Additionally, we found that inducing opto-LTP in non-stressed rats produced deficits in reversal learning similar to those seen in rats after CIC stress. Finally, CIC stress produced complex subregion-specific changes in dendritic material and spine subtype composition in the OFC. These results indicate that the effects of stress on plasticity in the OFC are distinct from those in the mPFC, and that the PFC should therefore not be treated as a homogenous region in studying either stress effects or potential treatments for stress-related psychiatric disorders.
| S-EPMC7739068 | biostudies-literature
Project description:Chronic stress is a key factor in the development of depression. It leads to hyperactivation of the hypothalamic-pituitary-adrenal (HPA) axis, which in turn increases the formation of glucocorticoids (GCs). Chronically elevated GC levels disrupt neuroplasticity and affect brain lipid metabolism, which may, ultimately, contribute to the development of depression. This study aimed to investigate the effects of the antidepressants St. John's Wort extract and escitalopram on lipid metabolism in vivo. Therefore, repeated corticosterone injections were used to induce depression-like behavior in rats. Male Sprague-Dawley rats were stressed with corticosterone injections (40 mg/kg, s.c.) over 22 consecutive days and were concomitantly treated with varying doses of the St. John's wort extract Ze 117 (30, 90 or 180 mg/kg, p.o.) or escitalopram (10 mg/kg, p.o.) and behavioral changes were evaluated using a modified forced swim test. The results indicate that repeated corticosterone injections significantly decreased the latency to first immobility. Furthermore, co-treatment of corticosterone with Ze 117 increased latency to first immobility significantly compared to rats treated with corticosterone alone. To further investigate the biochemical effects of corticosterone-induced stress, as well as the possible counter-regulation by antidepressants, the lipidomes of the plasma and hippocampus samples were analyzed by shotgun mass spectrometry. Corticosterone-induced stress significantly altered key lipid metabolites in the plasma but not in the hippocampal samples. In the hippocampus, however, specific glycerophospholipids such as lysophosphatidylethanolamines (LPEs) increased with escitalopram treatment and with Ze 117, both showing significant correlations with behavioral parameters. In summary, our study shows significant behavioral- and lipidome-altering processes with Ze 117 and escitalopram in rat plasma and hippocampal samples, thereby providing new targets and biomarker ideas for clinical diagnosis and antidepressant intervention.
| S-EPMC11641671 | biostudies-literature