Molecular mechanism for stress-induced depression assessed by sequencing miRNA and mRNA in medial prefrontal cortex
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PROVIDER: PRJNA322051 | ENA |
REPOSITORIES: ENA
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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:In this study, we used chronic restraint stress to establish a mouse model of depression, and differentially expressed proteins in the medial prefrontal cortex of depressive model mice were detected by TMT proteomics. By functional enrichment analysis of the differentially expressed proteins, we found that CRS-induced mice have altered synaptic function and excessive autophagy. In addition, we also demonstrated that CRS may disrupt synaptic plasticity by affecting activation of the Wnt2b/尾-catenin pathway which may help explain the pathogenesis of depression and identify new antidepressant drug targets.
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Project description:To understand the consequences of chronic exposure to fluoxetine during postnatal life on global transcriptional changes withing the rat medial prefrontal cortex in adulthood. To understand the consequences of chronic exposure to fluoxetine during postnatal life on global transcriptional changes withing the rat medial prefrontal cortex in adulthood.
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Project description:Animal models provide opportunity to study neurobiological aspects of human alcoholism. Changes in gene expression have been implicated in mediating brain function, including reward system and addiction. The current study aimed to identify novel genes that may underlie ethanol preference. Microarray analysis comparing gene expression in nucleus accumbens (NAc), hippocampus (HP) and prefrontal medial cortex (mPFC) was performed in two rat strains selected for extreme levels of ethanol preference - Warsaw High Preferring (WHP) and Warsaw Low Preferring (WLP). The identified candidate genes may underlie differential ethanol preference in rat model of alcoholism. This is analysis of 18 RNA samples, including 9 technical replicates. Two strains of rats selected for extreme levels of ethanol preference (low preferring WLP and high preferring WHP) were compared. Three brain areas (nucleus accumbens, prefrontal medial cortex and hippocampus) were studied. For each brain area, 6 RNA samples (including 3 technical replicates) were analyzed. Each RNA sample consist of of equal amounts of total RNA from 3 male rats. Comparisons: Nucleus accumbens of WHP vs. Nucleus accumbens of WLP; Prefrontal medial cortex of WHP vs. Prefrontal medial cortex of WLP; Hippocampus of WHP vs. Hippocampus of WLP. 3 biological replicates in each comparison.
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Project description:To gain insight into the potential role of miRNA in major depressive disorder, in this study we assessed global expression of miRNAs in the ventrolateral prefrontal cortex (PFC) of depressed individuals in comparison to psychiatrically healthy controls. Our screening pointed to miR-1202, a miRNA specific to primates and enriched in the human brain. We validated our findings using quantitative real-time PCR and identified target genes of the differentially expressed miRNAs using bioinformatics analysis. MiR-1202 interacts with and regulates the expression of the metabotropic glutamate receptor 4 (GRM4) gene, and it responds to antidepressant treatment. These results suggest that miR-1202 is associated with the pathophysiology of depression, and is a potential target for novel antidepressant treatments. We assessed the global expression pattern of miRNAs in the ventrolateral PFC of depressed individuals (n = 14) in comparison with psychiatrically healthy controls (n = 11) using the Agilent human miRNA microarrays. Statistical analysis after multiple test correction identified miR-1202 as the most significantly dysregulated miRNA, with levels down-regulated in depressed brains. We validated the microarray miR-1202 findings by qRT-PCR using TaqMan probes, and found consistent results across the two expression analysis methods.
2014-05-30 | E-GEOD-58105 | biostudies-arrayexpress
Project description:To gain insight into the potential role of miRNA in major depressive disorder, in this study we assessed global expression of miRNAs in the ventrolateral prefrontal cortex (PFC) of depressed individuals in comparison to psychiatrically healthy controls. Our screening pointed to miR-1202, a miRNA specific to primates and enriched in the human brain. We validated our findings using quantitative real-time PCR and identified target genes of the differentially expressed miRNAs using bioinformatics analysis. MiR-1202 interacts with and regulates the expression of the metabotropic glutamate receptor 4 (GRM4) gene, and it responds to antidepressant treatment. These results suggest that miR-1202 is associated with the pathophysiology of depression, and is a potential target for novel antidepressant treatments.
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Project description:The transition to motherhood involves CNS changes that modify sociability and affective state. However, these changes also put females at risk for postpartum depression and psychosis, which impairs parenting abilities and adversely affects children. Thus, changes in expression and interactions in a core subset of genes may be critical for emergence of a healthy maternal phenotype, but inappropriate changes of the same genes could put women at risk for postpartum disorders. This study evaluated microarray gene expression changes in medial prefrontal cortex (mPFC), a region implicated in both maternal behavior and psychiatric disorders. Postpartum mice were compared to virgin controls housed with females and isolated for identical durations. Using the Modular Single-set Enrichment Test (MSET), we found that the genetic landscape of maternal mPFC bears statistical similarity to gene databases associated with schizophrenia (5 of 5 sets) and bipolar disorder (BPD, 3 of 3 sets). In contrast to previous studies of maternal lateral septum and medial preoptic area, enrichment of autism and depression-linked genes was not significant (2 of 9 sets, 0 of 4 sets). Among genes linked to multiple disorders were fatty acid binding protein 7 (Fabp7), glutamate metabotropic receptor 3 (Grm3), platelet derived growth factor, beta polypeptide (Pdgfrb), and nuclear receptor subfamily 1, group D, member 1 (Nr1d1). RT-qPCR confirmed these gene changes as well as FMS-like tyrosine kinase 1 (Flt1) and proenkephalin (Penk). Systems-level methods revealed involvement of developmental gene networks in establishing the maternal phenotype and indirectly suggested a role for numerous microRNAs and transcription factors in mediating expression changes. Together, this study suggests that a subset of genes involved in shaping the healthy maternal brain may also be dysregulated in mental health disorders and put females at risk for postpartum psychosis with aspects of schizophrenia and BPD. In total, 10 total RNA samples derived from micropunched medial prefrontal cortex were used for microarray analysis: 5 samples from lactating maternal mice (maternal) and 5 samples from age-matched virgin mice (virgin). All samples are biological replicates.
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