Expression data from brain parts (amygdala, hippocampus, prefrontal cortex, and cerebral cortex) from mice with or without chronic mild stress (CMS) treatments.
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE151807 | GEO | 2020/06/05
REPOSITORIES: GEO
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Project description:Major depressive disorder (MDD) is a prevalent and life-threatening illness in modern society. The susceptibility to MDD is profoundly influenced by environmental factors, such as stressful lifestyle or traumatic events, which could impose maladaptive transcriptional program through epigenetic regulation. However, the underlying molecular mechanisms remain elusive. Here we report that stress-susceptible rodents exhibit lower levels of histone crotonylation in the medial prefrontal cortex (mPFC), concurrent with regional upregulation of chromodomain Y-like (CDYL), a crotonyl-CoA hydratase and histone methyllysine reader. Overexpression of CDYL in the prelimbic cortex (PL), a sub-region of mPFC, increases microdefeat-induced social avoidance behaviors and anhedonia in mice. Conversely, knockdown of CDYL in PL prevents chronic social defeat stress-induced depression-like behaviors. Mechanistically, we show that CDYL inhibits structural synaptic plasticity mainly by transcriptional repression of neuropeptide VGF, and this activity is dependent on its dual effect on regional histone crotonylation and H3K27 tri-methylation on the VGF promoter. Together, our data indicate CDYL plays a critical role in regulating stress-induced depression-like behaviors, providing a potential therapeutic target for MDD.
2018-11-15 | GSE120293 | GEO
Project description:Major depressive disorder (MDD) is a clinically defined entity with little understanding as to the underlying pathological substrate. Biologically, MDD is characterized by disruption of neurotransmitters, especially serotonin and noradrenaline, which are the main targets of antidepressants. We previously demonstrated significant reduction of glial cell number in the cingulate and dorsolateral prefrontal cortical regions. Unfortunately, individuals living with HIV still have very high rates of MDD, despite the fact that mortality rates have fallen sharply with effective antiretroviral treatment. It is possible that in this treatment era, living with chronic HIV infection may result in long-term neuropathological changes that predispose to MDD. For example, it is known that HIV is associated with a range of inflammatory pathologies, neuronal loss, and dendrite-synaptic damage. In HIV, these neurodegenerative changes have been linked to neurocognitive impairments, however it is also possible that these changes potentiate MDD. In the current study, we sought to determine whether there are changes in gene expression in the MDD brain in the frontal cortex in HIV-context. We identify a large number of genes dysregulated at p<0.05 significance. Retrospective gene expression analysis of autopsy brain tissue. Four HIV/MDD subjects are identified and age-matched HIV patients without neuropsychiatric conditions are compared as controls.
2010-02-01 | E-GEOD-17440 | biostudies-arrayexpress
Project description:Expression data from brain parts (amygdala, hippocampus, prefrontal cortex, and cerebral cortex) from mice with or without chronic mild stress (CMS) treatments.
| PRJNA637312 | ENA
Project description:Major depressive disorder (MDD) is a common disorder and is responsible for considerable disability in global functioning, anorexia, and severer medical comorbidity. Recently, some reports showed the relationship between MDD and the metabolic disorders such as diabetes. We examined gene expression profiles in the mice prefrontal cortex using genome-wide microarray technology, and determined gene expression profiles with and without chronic mild stress(CMS) for 4 weeks which was often used to make models of depression. To analyze the candidate genes involved in not only depression but dysfunction of physiological homeostasis like diabetes, we campared the gene expression levels between with and without CMS, then we isolated 494 genes showing a more than 2-fold increase or a less than 1/2-fold decrease, in addition, we chose the isolated genes transcriptional products of both samples were confirmed clearly. The prefrontal cortex of C57Bl/6 N sea mice with and without CMS. We mixed tatal RNA from 7 mice prefrontal cortex per each.
2014-02-28 | E-GEOD-49867 | biostudies-arrayexpress
Project description:Major depressive disorder (MDD) is a clinically defined entity with little understanding as to the underlying pathological substrate. Biologically, MDD is characterized by disruption of neurotransmitters, especially serotonin and noradrenaline, which are the main targets of antidepressants. We previously demonstrated significant reduction of glial cell number in the cingulate and dorsolateral prefrontal cortical regions. Unfortunately, individuals living with HIV still have very high rates of MDD, despite the fact that mortality rates have fallen sharply with effective antiretroviral treatment. It is possible that in this treatment era, living with chronic HIV infection may result in long-term neuropathological changes that predispose to MDD. For example, it is known that HIV is associated with a range of inflammatory pathologies, neuronal loss, and dendrite-synaptic damage. In HIV, these neurodegenerative changes have been linked to neurocognitive impairments, however it is also possible that these changes potentiate MDD. In the current study, we sought to determine whether there are changes in gene expression in the MDD brain in the frontal cortex in HIV-context. We identify a large number of genes dysregulated at p<0.05 significance.
2010-02-01 | GSE17440 | GEO
Project description:Purpose: Major depressive disorder (MDD) is a worldwide concern and devastating psychiatric disease. The World Health Organization claims that MDD leads to at least 11.9% of the global burden of disease. However, the underlying pathophysiology mechanisms of MDD remain largely unknown. Experimental design: Herein, we used a proteomic-based strategy to compare the prefrontal cortex (PFC) in chronic social defeat stress (CSDS) model mice with a control group. Based on pooled samples, differential proteins were identified in the PFC proteome using iTRAQ coupled with LC-MS/MS. Results: Ingenuity Pathway Analysis (IPA) was then followed to predict relevant pathways, with the ephrin receptor signaling pathway selected for further research. Additionally, as the selected key proteins of the ephrin receptor signaling pathway, ephrin type-B receptor 6 (EphB6) and the ERK pathway were validated by western blotting. Conclusion and clinical relevant: Altogether, increased understanding of the ephrin receptor signaling pathway in MDD is provided, which implicates further investigation of PFC dysfunction induced by CSDS treatment.
2018-07-05 | PXD007573 | Pride
Project description:Major depressive disorder (MDD) exhibits numerous clinical, epidemiological, and molecular features that are consistent with partially inherited and partially acquired epigenetic misregulation. We performed microarray based DNA modification study of MDD, utilizing affected and unaffected samples from white blood cells from monozygotic twins discordant for MDD, post-mortem prefrontal cortex tissues, and sperm samples. We performed DNA methylome analysis on white blood cells from monozygotic twins discordant for depression (n=200), pre-frontal cortex (n=71), and germline samples (n=33) from affected individuals and controls (total n=304). DNA samples were enriched for unmodified fraction of the genome using DNA-modification sensitive restriction enzyme digestion followed by adaptor-mediated PCR. The enriched fractions were labelled with a fluorescent dye (Cy5) and hybridized onto the array with a common reference pool (Cy3) generated from individuals unrelated to this study.
2012-04-27 | E-GEOD-37579 | biostudies-arrayexpress
Project description:Overall risk for Major Depressive Disorder (MDD) is determined by complex interactions between genetic and environmental factors that influence epigenetic regulation of neuroplasticity and stress pathways1,2. These mechanisms are specific to the distinct regulatory context within regionally-defined brain cell-types3,4. Here, we employed genome-wide chromatin accessibility profiling of neuronal vs. non-neuronal cells in orbitofrontal cortex (OFC) to capture regulatory signatures of MDD. We mapped genetic risk for MDD to active promoters of non-neuronal cell-types in OFC and identified MDD-specific open chromatin regions, which were differentially accessible exclusively in non-neuronal cells. Characterization of these loci revealed a key role for astrocyte dysfunction, and implicated the chromatin remodeling protein ZBTB7A, which coordinates wide-ranging cellular activation programs, including NF-kB inflammatory transcription5. In mice, astrocyte-specific knockdown of Zbtb7a reversed chromatin remodeling, reactive astrocyte transcription, and behavioral deficits associated with chronic stress. Conversely, ZBTB7A overexpression in OFC astrocytes induced stress-related behavioral deficits, promoted widespread inflammatory gene expression, and drove pathophysiological OFC neuronal hyperactivity in response to a mild subthreshold stressor. Our data highlight a critical role for OFC astrocytes in the bidirectional regulation of stress vulnerability and pinpoint ZBTB7A as a key factor mediating maladaptive astrocyte plasticity and OFC neuronal hyperexcitability in MDD.
2023-08-08 | GSE214921 | GEO
Project description:Overall risk for Major Depressive Disorder (MDD) is determined by complex interactions between genetic and environmental factors that influence epigenetic regulation of neuroplasticity and stress pathways1,2. These mechanisms are specific to the distinct regulatory context within regionally-defined brain cell-types3,4. Here, we employed genome-wide chromatin accessibility profiling of neuronal vs. non-neuronal cells in orbitofrontal cortex (OFC) to capture regulatory signatures of MDD. We mapped genetic risk for MDD to active promoters of non-neuronal cell-types in OFC and identified MDD-specific open chromatin regions, which were differentially accessible exclusively in non-neuronal cells. Characterization of these loci revealed a key role for astrocyte dysfunction, and implicated the chromatin remodeling protein ZBTB7A, which coordinates wide-ranging cellular activation programs, including NF-kB inflammatory transcription5. In mice, astrocyte-specific knockdown of Zbtb7a reversed chromatin remodeling, reactive astrocyte transcription, and behavioral deficits associated with chronic stress. Conversely, ZBTB7A overexpression in OFC astrocytes induced stress-related behavioral deficits, promoted widespread inflammatory gene expression, and drove pathophysiological OFC neuronal hyperactivity in response to a mild subthreshold stressor. Our data highlight a critical role for OFC astrocytes in the bidirectional regulation of stress vulnerability and pinpoint ZBTB7A as a key factor mediating maladaptive astrocyte plasticity and OFC neuronal hyperexcitability in MDD.
2023-08-08 | GSE214919 | GEO
Project description:Overall risk for Major Depressive Disorder (MDD) is determined by complex interactions between genetic and environmental factors that influence epigenetic regulation of neuroplasticity and stress pathways1,2. These mechanisms are specific to the distinct regulatory context within regionally-defined brain cell-types3,4. Here, we employed genome-wide chromatin accessibility profiling of neuronal vs. non-neuronal cells in orbitofrontal cortex (OFC) to capture regulatory signatures of MDD. We mapped genetic risk for MDD to active promoters of non-neuronal cell-types in OFC and identified MDD-specific open chromatin regions, which were differentially accessible exclusively in non-neuronal cells. Characterization of these loci revealed a key role for astrocyte dysfunction, and implicated the chromatin remodeling protein ZBTB7A, which coordinates wide-ranging cellular activation programs, including NF-kB inflammatory transcription5. In mice, astrocyte-specific knockdown of Zbtb7a reversed chromatin remodeling, reactive astrocyte transcription, and behavioral deficits associated with chronic stress. Conversely, ZBTB7A overexpression in OFC astrocytes induced stress-related behavioral deficits, promoted widespread inflammatory gene expression, and drove pathophysiological OFC neuronal hyperactivity in response to a mild subthreshold stressor. Our data highlight a critical role for OFC astrocytes in the bidirectional regulation of stress vulnerability and pinpoint ZBTB7A as a key factor mediating maladaptive astrocyte plasticity and OFC neuronal hyperexcitability in MDD.
2023-08-08 | GSE214920 | GEO