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ABSTRACT:
PROVIDER: PRJNA734369 | ENA |
REPOSITORIES: ENA
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Project description:We performed high-throughput profiling of gene expression in rat hippocampus in response to chronic unpredictable mild stress (CUMS) and albiflorin treatment. Total 415 differentially expressed genes (DEGs) were identified in rat hippocampus in response to albiflorin treatment compared with CUMS rats treated with saline (CUMS-Sal). We conducted the integrated metabolomics and transcriptomics analysis and found the correction of 16 biochemical pathways by albiflorin such as sphingolipids, phospholipids, tryptophan metabolism, fatty acid oxidation, and purine and pyrimidine metabolism. Our study provided deep insights into the understanding of the molecular mechanisms underlying the rapid antidepressant actions of albiflorin.
2018-01-20 | GSE109445 | GEO
Project description:Major depressive disorder is a common mood disorder. Chronic stressful life is presumably main etiology that leads to the neuron and synapse atrophies in the limbic system. However, the intermediate molecules from stress to neural atrophy remain elusive. Mice were treated by chronic unpredictable mild stress (CUMS) until demonstrating depression-like behaviors confirmed by the tests of sucrose preference, forced swimming and Y-maze. The sequencings of microRNA and mRNA from the medial prefrontal cortices were performed in CUMS-induced depression mice versus control mice to assess the molecular profiles of major depressive disorder. In the medial prefrontal cortices of depression-like mice, the levels of mRNAs that translated the proteins for the GABAergic synapses, dopaminergic synapses, myelination, synaptic vesicle cycle and neuronal growth were downregulated. miRNAs of regulating these mRNAs are upregulated. The deterioration of GABAergic and dopaminergic synapses as well as axonal growth is associated to CUMS-induced depression.
2017-02-09 | GSE81588 | GEO
Project description:Major depressive disorder is a common mood disorder. Chronic stressful life is presumably main etiology that leads to the neuron and synapse atrophies in the limbic system. However, the intermediate molecules from stress to neural atrophy remain elusive. Mice were treated by chronic unpredictable mild stress (CUMS) until demonstrating depression-like behaviors confirmed by the tests of sucrose preference, forced swimming and Y-maze. The sequencings of microRNA and mRNA from the medial prefrontal cortices were performed in CUMS-induced depression mice versus control mice to assess the molecular profiles of major depressive disorder. In the medial prefrontal cortices of depression-like mice, the levels of mRNAs that translated the proteins for the GABAergic synapses, dopaminergic synapses, myelination, synaptic vesicle cycle and neuronal growth were downregulated. miRNAs of regulating these mRNAs are upregulated. The deterioration of GABAergic and dopaminergic synapses as well as axonal growth is associated to CUMS-induced depression.
2017-02-09 | GSE81587 | GEO
Project description:It remains unclear why many patients with depression do not respond to antidepressant treatment. In three cohorts of individuals with depression and treated with serotonin-norepinephrine reuptake inhibitor (N=424) we show that responders, but not non-responders, display an increase of GPR56 mRNA in the blood. In a small group of subjects we also show that GPR56 is also downregulated in the PFC of individuals with depression that died by suicide. In mice, we show that chronic stress induced Gpr56 downregulation in the blood and prefrontal cortex (PFC), which is accompanied by depression-like behaviour, and can be reversed by antidepressant treatment. Gpr56 knockdown in mouse PFC was is associated with depressive-like behaviors, executive dysfunction and poor response to antidepressant treatment. GPR56 peptide agonists had antidepressant-like effects and up-regulated AKT/GSK3/EIF4 pathways. Our findings uncover a potential role of GPR56 in antidepressant response.
2020-03-31 | GSE146446 | GEO
Project description:Background: Examining transcriptional regulation by existing antidepressants in key neural circuits implicated in depression, and understanding the relationship to transcriptional mechanisms of susceptibility and natural resilience, may help in the search for new therapeutics. Further, given the heterogeneity of treatment response in human populations, examining both treatment response and non-response is critical. Methods: We compared the effects of a conventional monoamine-based tricyclic antidepressant, imipramine (14 daily injections), and a rapidly acting, experimental, non-monoamine-based antidepressant, ketamine (single injection), in mice subjected to chronic social defeat stress, a validated model of depression, and used RNA-sequencing to analyze transcriptional profiles associated with susceptibility, resilience and antidepressant response and non-response in prefrontal cortex (PFC), nucleus accumbens, hippocampus, and amygdala. Results: We identified approximately equal numbers of responder and non-responder mice following ketamine or imipramine treatment. Ketamine induced more expression changes in hippocampus than other brain regions; imipramine induced more expression changes in nucleus accumbens and amygdala. Transcriptional profiles in ketamine and imipramine responders were most similar in PFC, where the least transcriptional regulation occurred for each drug. Non-response reflected both the lack of response-associated gene expression changes and unique gene regulation. In responders, both drugs reversed susceptible associated transcriptional changes as well as induced resilient associated transcription in PFC, with effects varying by drug and brain region studied. Conclusions: We generated a uniquely large resource of gene expression data in four inter-connected limbic brain regions implicated in depression and its treatment with imipramine or ketamine. Our analyses highlight the PFC as a key site of common transcriptional regulation by both antidepressant drugs and in both reversing susceptibility and inducing resilience associated molecular adaptations. In addition, we found region-specific effects of each drug suggesting both common and unique effects of imipramine versus ketamine. mRNA profiles of susceptibility to chronic social defeat stress as well as treatment response were generated across 4 separate brain regions, with a sample size of 3-5 per group.
2016-07-27 | E-GEOD-81672 | biostudies-arrayexpress
Project description:To explored the mechanism of pharmacokinetic perturbation in chronic unpredicted mild stress (CUMS) resulting depression, CUMS-induced depression animal model with spontaneous diabetic GK rats were established. The expression profile in GK rats' livers were screened using Affymetrix Rat 230 2.0 Array.
2017-09-25 | GSE94988 | GEO
Project description:Selective serotonin reuptake inhibitors (SSRIs) such as fluoxetine are the most common treatment for major depression. However, approximately 50% of depressed patients fail to achieve an effective treatment response. Understanding how gene expression systems relate to treatment responses may be critical for understanding antidepressant resistance. Transcriptome profiling allows for the simultaneous measurement of expression levels for thousands of genes and the opportunity to utilize this information to determine mechanisms underlying antidepressant treatment responses. However, the best way to relate this immense amount of information to treatment resistance remains unclear. We take a novel approach to this question by examining dentate gyrus transcriptomes from the perspective of a stereotyped fluoxetine-induced gene expression program. Expression programs usually represent stereotyped changes in expression levels that occur as cells transition phenotypes. Fluoxetine will shift transcriptomes so they lie somewhere between a baseline state and a full-response at the end of the program. The position along this fluoxetine-induced gene expression program (program status) was measured using principal components analysis (PCA). The same expression program was initiated in treatment-responsive and resistant mice but treatment response was associated with further progression along the fluoxetine-induced gene expression program. The study of treatment-related differences in gene expression program status represents a novel way to conceptualize differences in treatment responses at a transcriptome level. Understanding how antidepressant-induced gene expression program progression is modulated represents an important area for future research and could guide efforts to develop novel augmentation strategies for antidepressant treatment resistant individuals. 38 samples, 2 dentate regions (dorsal/ventral), 3 groups (control, antidepressant resistant (4 mice), antidepressant responsive (7 mice), untreated (8 mice).
2013-12-31 | E-GEOD-43261 | biostudies-arrayexpress
Project description:Background: Examining transcriptional regulation by existing antidepressants in key neural circuits implicated in depression, and understanding the relationship to transcriptional mechanisms of susceptibility and natural resilience, may help in the search for new therapeutics. Further, given the heterogeneity of treatment response in human populations, examining both treatment response and non-response is critical. Methods: We compared the effects of a conventional monoamine-based tricyclic antidepressant, imipramine (14 daily injections), and a rapidly acting, experimental, non-monoamine-based antidepressant, ketamine (single injection), in mice subjected to chronic social defeat stress, a validated model of depression, and used RNA-sequencing to analyze transcriptional profiles associated with susceptibility, resilience and antidepressant response and non-response in prefrontal cortex (PFC), nucleus accumbens, hippocampus, and amygdala. Results: We identified approximately equal numbers of responder and non-responder mice following ketamine or imipramine treatment. Ketamine induced more expression changes in hippocampus than other brain regions; imipramine induced more expression changes in nucleus accumbens and amygdala. Transcriptional profiles in ketamine and imipramine responders were most similar in PFC, where the least transcriptional regulation occurred for each drug. Non-response reflected both the lack of response-associated gene expression changes and unique gene regulation. In responders, both drugs reversed susceptible associated transcriptional changes as well as induced resilient associated transcription in PFC, with effects varying by drug and brain region studied. Conclusions: We generated a uniquely large resource of gene expression data in four inter-connected limbic brain regions implicated in depression and its treatment with imipramine or ketamine. Our analyses highlight the PFC as a key site of common transcriptional regulation by both antidepressant drugs and in both reversing susceptibility and inducing resilience associated molecular adaptations. In addition, we found region-specific effects of each drug suggesting both common and unique effects of imipramine versus ketamine.
2016-07-27 | GSE81672 | GEO
Project description:Accumulating evidence demonstrates that the gut microbiota affects brain function and behavior, including depressive behavior. Antidepressants are the main drugs used for treatment of depression. We hypothesized that antidepressant treatment could modify gut microbiota which can partially mediate their antidepressant effects. Mice were chronically treated with one of five antidepressants (fluoxetine, escitalopram, venlafaxine, duloxetine or desipramine), and gut microbiota was analyzed, using 16s rRNA gene sequencing. After characterization of differences in the microbiota, chosen bacterial species were supplemented to vehicle and antidepressant-treated mice, and depressive-like behavior was assessed to determine bacterial effects. RNA-seq analysis was performed to determine effects of bacterial treatment in the brain. Antidepressants reduced richness and increased beta diversity of gut bacteria, compared to controls. At the genus level, antidepressants reduced abundances of Ruminococcus, Adlercreutzia, and an unclassified Alphaproteobacteria. To examine implications of the dysregulated bacteria, we chose one of antidepressants (duloxetine) and investigated if its antidepressive effects can be attenuated by simultaneous treatment with Ruminococcus flavefaciens or Adlercreutzia equolifaciens. Supplementation with R. flavefaciens diminished duloxetine-induced decrease in depressive-like behavior, while A. equolifaciens had no such effect. R. flavefaciens treatment induced changes in cortical gene expression, up-regulating genes involved in mitochondrial oxidative phosphorylation, while down-regulating genes involved in neuronal plasticity. Our results demonstrate that various types of antidepressants alter gut microbiota composition, and further implicate a role for R. flavefaciens in alleviating depressive-like behavior.
2019-04-05 | GSE129359 | GEO