Molecular mechanism for stress-induced depression assessed by sequencing miRNA and mRNA in medial prefrontal cortex
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE81590 | GEO | 2017/02/09
SECONDARY ACCESSION(S): PRJNA322051
REPOSITORIES: GEO
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Project description:BackgroundMajor depression is a prevalent mood disorder. Chronic stress is presumably main etiology that leads to the neuron and synapse atrophies in the limbic system. However, the intermediate molecules from stresses to neuronal atrophy remain elusive, which we have studied in the medial prefrontal cortices from depression mice.Methods and resultsThe mice were treated by the chronic unpredictable mild stress (CUMS) until they expressed depression-like behaviors confirmed by the tests of sucrose preference, forced swimming and Y-maze. High-throughput sequencings of microRNA and mRNA in the medial prefrontal cortices were performed in CUMS-induced depression mice versus control mice to demonstrate the molecular profiles of major depression. 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.ConclusionThe deteriorations of GABAergic and dopaminergic synapses as well as axonal growth are associated with CUMS-induced depression.
| S-EPMC4948880 | biostudies-literature
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:Molecular mechanism for stress-induced depression assessed by sequencing miRNA and mRNA in medial prefrontal cortex
| PRJNA322051 | ENA
Project description:Functional lateralization of the prefrontal cortex has been implicated in stress and emotional disorders, yet underlying gene expression changes remains unknown. Here, we report molecular signatures lateralized by chronic social defeats between the two medial prefrontal cortices (mPFCs). Stressed mice show 526 asymmetrically expressed genes between the mPFCs. This cortical asymmetry selectively occurs in stressed mice with depressed social activity, but not in resilient mice with normal behavior. We have isolated highly asymmetric genes including connective tissue growth factor (CTGF), a molecule that modulates wound healing at the periphery. Knockdown of CTGF gene in the right mPFC by shRNA led to a stress-resistant behavioral phenotype. Overexpression of CTGF in the right mPFC using viral transduction induces social avoidance while the left mPFC thereof prevent stress-induced social avoidance. Our study provides a molecular window into the mechanism of stress-induced socioemotional disorders, which can pave the way for new interventions by targeting cortical asymmetry.
| S-EPMC8201740 | biostudies-literature
Project description:BackgroundEmerging evidence has highlighted the moderating effect of childhood maltreatment (CM) in shaping neurobiological abnormalities in major depressive disorder (MDD). However, whether neural mechanisms underlying stress sensitivity in MDD are affected by the history of CM is unclear.MethodsTwo hundred and thirteen medication-free female participants were recruited for a functional magnetic resonance imaging study assessing the effects of psychosocial stress on neural responses. The Montreal Imaging Stress Task was administrated to 44 female MDD patients with CM (MDD/CM), 32 female MDD patients without CM (MDD/noCM), 43 female healthy controls (HCs) with CM (HC/CM), and 94 female HCs without CM (HC/noCM). A CM (CM, noCM) × diagnosis (MDD, HC) whole-brain voxel-wise analysis was run to assess putative group differences in neural stress responses.ResultsA significant CM × Diagnosis interaction emerged in the medial prefrontal cortex (mPFC). Bonferroni-corrected simple effects analysis clarified that (1) the MDD/CM group had less mPFC deactivation than the HC/CM group, (2) the MDD/noCM group exhibited greater mPFC deactivation than the HC/noCM group, and (3) the MDD/CM group exhibited less mPFC deactivation relative to the MDD/noCM group. In addition, the mPFC-seed psychophysiological interaction analysis revealed that individuals in the CM groups had significantly greater stress-related mPFC-left superior frontal gyrus and mPFC-right posterior cerebellum connectivity relative to the noCM groups.ConclusionsFindings highlight distinct neural abnormalities in MDD depending on prior CM history, particularly potentiated stress-related mPFC recruitment among MDD individuals reporting CM. Moreover, CM history was generally associated with the disruption in functional connectivity centered on the mPFC.
| S-EPMC9063172 | biostudies-literature
Project description:The ephrin B2 (EphB2) receptor is a tyrosine kinase receptor that is associated with synaptic development and maturation. It has recently been implicated in cognitive deficits and anxiety. However, still unknown is the involvement of EphB2 in the vulnerability to stress. In the present study, we observed decreases in EphB2 levels and their downstream molecules in the medial prefrontal cortex (mPFC) but not in the orbitofrontal cortex (OFC) in mice that were susceptible to chronic social defeat stress. The activation of EphB2 receptors with EphrinB1-Fc in the mPFC produced stress-resistant and antidepressant-like behavioral effects in susceptible mice that lasted for at least 10 days. EphB2 receptor knockdown by short-hairpin RNA in the mPFC increased the susceptibility to stress and induced depressive-like behaviors in a subthreshold chronic social defeat stress paradigm. These behavioral effects were associated with changes in the phosphorylation of cofilin and membrane ?-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) trafficking and the expression of some synaptic proteins in the mPFC. We also found that EphB2 regulated stress-induced spine remodeling in the mPFC. Altogether, these results indicate that EphB2 is a critical regulator of stress vulnerability and might be a potential target for the treatment of depression.
| S-EPMC4987853 | biostudies-literature
Project description:Following publication of the above article, the authors noticed that an incorrect version of Figs. 2f, 3f, 5h and 7d was presented.
| S-EPMC6784905 | biostudies-literature
Project description:BACKGROUND:Pathophysiology models of major depression (MD) center on the dysfunction of various cortical areas within the orbital and medial prefrontal cortex. While independent structural and functional abnormalities in these areas are consistent findings in MD, the complex interactions among them and the rest of the cortex remain largely unexplored. METHODS:We used resting-state functional magnetic resonance imaging connectivity to systematically map alterations in the communication between orbital and medial prefrontal cortex fields and the rest of the brain in MD. Functional connectivity (FC) maps from participants with current MD (n = 35), unaffected first-degree relatives (n = 36), and healthy control subjects (n = 38) were subjected to conjunction analyses to distinguish FC markers of MD vulnerability and FC markers of MD disease. RESULTS:FC abnormalities in MD vulnerability were found for dorsal medial wall regions and the anterior insula and concerned altered communication of these areas with the inferior parietal cortex and dorsal posterior cingulate, occipital areas and the brainstem. FC aberrations in current MD included the anterior insula, rostral and dorsal anterior cingulate cortex, and lateral orbitofrontal areas and concerned altered communication with the dorsal striatum, the cerebellum, the precuneus, the anterior prefrontal cortex, somatomotor cortex, dorsolateral prefrontal cortex, and visual areas in the occipital and inferior temporal lobes. CONCLUSIONS:Functionally delineated parcellation maps can be used to identify putative connectivity markers in extended cortical regions such as the orbital and medial prefrontal cortex. The anterior insula and the rostral anterior cingulate cortex play a central role in the pathophysiology of MD, being consistently implicated both in the MD vulnerability and MD disease states.
| S-EPMC5894884 | biostudies-literature
Project description:Anatomical alterations in the medial prefrontal cortex (mPFC) are associated with hypothalamopituitary adrenal (HPA) axis dysregulation, altered stress hormone levels, and psychiatric symptoms of stress-related mental illnesses. Functional imaging studies reveal impairment and shrinkage of the mPFC in such conditions, and these findings are paralleled by experimental studies showing dendritic retraction and spine loss following repeated stress in rodents. Here we extend this characterization to how repeated stress affects dendritic spine morphology in mPFC through the utilization of an automated approach that rapidly digitizes, reconstructs three dimensionally, and calculates geometric features of neurons. Rats were perfused after being subjected to 3 weeks of daily restraint stress (6 hours/day), and intracellular injections of Lucifer Yellow were made in layer II/III pyramidal neurons in the dorsal mPFC. To reveal spines in all angles of orientation, deconvolved high-resolution confocal laser scanning microscopy image stacks of dendritic segments were reconstructed and analyzed for spine volume, surface area, and length using a Rayburst-based automated approach (8,091 and 8,987 spines for control and stress, respectively). We found that repeated stress results in an overall decrease in mean dendritic spine volume and surface area, which was most pronounced in the distal portion of apical dendritic fields. Moreover, we observed an overall shift in the population of spines, manifested by a reduction in large spines and an increase in small spines. These results suggest a failure of spines to mature and stabilize following repeated stress and are likely to have major repercussions on function, receptor expression, and synaptic efficacy.
| S-EPMC2796421 | biostudies-literature