Ontology highlight
ABSTRACT:
PROVIDER: PRJNA1138305 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR29906468_1.fastq.gz | Fastqsanger.gz | |||
| SRR29906468_2.fastq.gz | Fastqsanger.gz | |||
| SRR29906469_1.fastq.gz | Fastqsanger.gz | |||
| SRR29906469_2.fastq.gz | Fastqsanger.gz | |||
| SRR29906470_1.fastq.gz | Fastqsanger.gz |
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Project description:Bipolar disorder is a complex polygenetic disorder that is characterized by recurrent episodes of depression and mania, the heterogeneity of which is likely complicated by epigenetic modifications that remain to be elucidated. Here, we performed transcriptomic analysis of peripheral blood RNA from monozygotic twins discordant for bipolar disorder and identified a bipolar disorder-associated upregulated long non-coding RNA (lncRNA), AP1AR-DT. We observed that overexpression of AP1AR-DT in the mouse medial prefrontal cortex (mPFC) resulted in a reduction of both the total spine density and the spontaneous excitatory postsynaptic current (sEPSC) frequency of mPFC neurons, as well as depressive and anxiety-like behaviors. A combination of the results of brain transcriptome analysis of AP1AR-DT overexpressing mice brains with the known genes associated with bipolar disorder revealed that NEGR1, which encodes neuronal growth regulator 1, is one of the AP1AR-DT targets and is reduced in vivo upon gain of AP1AR-DT in mice. The results of the present study demonstrated that overexpression of recombinant Negr1 in the mPFC neurons of AP1AR-DTOE mice ameliorates depressive and anxiety-like behaviors and normalizes the reduced excitatory synaptic transmission induced by the gain of AP1AR-DT. Furthermore, the study provides evidence that AP1AR-DT reduces NEGR1 expression by competing for the transcriptional activator NRF1 in the overlapping binding site of the NEGR1 promoter region. The epigenetic and pathophysiological mechanism linking AP1AR-DT to the modulation of excitatory synaptic function provides etiological implications for bipolar disorder.
2024-07-22 | GSE272753 | GEO
Project description:Bipolar disorder is a complex polygenetic disorder that is characterized by recurrent episodes of depression and mania, the heterogeneity of which is likely complicated by epigenetic modifications that remain to be elucidated. Here, we performed transcriptomic analysis of peripheral blood RNA from monozygotic twins discordant for bipolar disorder and identified a bipolar disorder-associated upregulated long non-coding RNA (lncRNA), AP1AR-DT. We observed that overexpression of AP1AR-DT in the mouse medial prefrontal cortex (mPFC) resulted in a reduction of both the total spine density and the spontaneous excitatory postsynaptic current (sEPSC) frequency of mPFC neurons, as well as depressive and anxiety-like behaviors. A combination of the results of brain transcriptome analysis of AP1AR-DT overexpressing mice brains with the known genes associated with bipolar disorder revealed that NEGR1, which encodes neuronal growth regulator 1, is one of the AP1AR-DT targets and is reduced in vivo upon gain of AP1AR-DT in mice. The results of the present study demonstrated that overexpression of recombinant Negr1 in the mPFC neurons of AP1AR-DTOE mice ameliorates depressive and anxiety-like behaviors and normalizes the reduced excitatory synaptic transmission induced by the gain of AP1AR-DT. Furthermore, the study provides evidence that AP1AR-DT reduces NEGR1 expression by competing for the transcriptional activator NRF1 in the overlapping binding site of the NEGR1 promoter region. The epigenetic and pathophysiological mechanism linking AP1AR-DT to the modulation of excitatory synaptic function provides etiological implications for bipolar disorder.
2024-07-22 | GSE272752 | GEO
Project description:Gain of bipolar disorder-related lncRNA AP1AR-DT in mice induces depressive and anxiety-like behaviors by reducing Negr1-mediated excitatory synaptic transmission [SK-N-SH RNA-seq]
| PRJNA1138663 | ENA
Project description:Stressful life events increase risk for depression, yet the molecular mechanisms by which stress is encoded in the brain to induce maladaptive behaviors are not well understood. Emerging evidence has shown that stress dysregulates gene expression in the brain, yet the cellular origin of these gene expression alterations has yet to be determined. To address this question, we used a chronic unpredictable stress (CUS) paradigm that drives depressive- and anxiety-like behaviors in male and female mice and single-nucleus transcriptomics to identify cell type-specific gene expression changes in the cortex. We find that neocortical excitatory neurons are particularly vulnerable to chronic stress exposure, and that CUS reprograms these cells to decrease transcription of synaptic genes involved in glutamatergic neurotransmission. We identify the ubiquitously expressed factor, Yin Yang 1 (YY1), as a key driver of the transcriptional reprogramming observed in excitatory neurons isolated from CUS mice. Selective depletion of YY1 in excitatory neurons of the prefrontal cortex (PFC) increases the stress sensitivity of mice, inducing depressive- and anxiety-related behaviors following an abbreviated stress exposure and deregulating expression of key stress-related genes in the PFC. Importantly, we find that YY1 functions in both males and females to facilitate stress coping. This work establishes a novel mechanism underlying chronic stress-induced behavior, in which epigenetic responses to stress in PFC excitatory neurons are mediated by stress-dependent YY1 activity. Our findings demonstrate how post-mitotic neurons adapt to stress experience and identify a novel molecular target that is generalizable to males and females for therapeutic treatment of stress-related neuropsychiatric disorders.
2021-11-19 | GSE145970 | GEO
Project description:RBFOX3 mutations are linked to epilepsy and cognitive impairments, but the underlying pathophysiology of these disorders is poorly understood. Here we report replication of human symptoms in a mouse model with disrupted Rbfox3. Rbfox3 knockout mice displayed increased seizure susceptibility and decreased anxiety-related behaviors. Focusing on hippocampal phenotypes, we found Rbfox3 knockout mice showed increased expression of plasticity genes Egr4 and Arc, and the synaptic transmission and plasticity were defective in the mutant perforant pathway. The mutant dentate granules cells exhibited an increased frequency, but normal amplitude, of excitatory synaptic events, and this change was associated with an increase in the neurotransmitter release probability and dendritic spine density. Together, our results demonstrate anatomical and functional abnormality in Rbfox3 knockout mice, and may provide mechanistic insights for RBFOX3-related human brain disorders. Two samples (one is from wild-type and the other is from Rbfox3 homozygous knockout mice)
2016-07-26 | E-GEOD-84786 | biostudies-arrayexpress
Project description:RNA was extracted from peripheral blood mononuclear cells (PBMC) of 24 adult healthy controls, 8 adult patients with bipolar disorder, and 21 adult patients with major depressive disorder to analyze gene expression patterns that identify biomarkers of disease and that may be correlated with fMRI data.
2012-07-26 | GSE39653 | GEO
Project description:Emerging high-throughput proteomic technologies have recently been considered as a powerful means of identifying substrates involved in mood disorders. We performed proteomic profiling using liquid chromatography-tandem mass spectrometry to identify dysregulated proteins in plasma samples of 44, 49, and 50 patients with major depressive disorder (MDD), bipolar disorder (BD), and schizophrenia , respectively, in comparison to 51 healthy controls (HCs).
2022-02-16 | PXD028841 | Pride
Project description:GAIN: Whole Genome Association Study of Bipolar Disorder
| PRJNA75403 | ENA
Project description:GAIN: Whole Genome Association Study of Bipolar Disorder
| PRJNA75401 | ENA
Project description:Both the amygdala and the bed nucleus of the stria terminalis (BNST) have been implicated in maladaptive anxiety characteristic of anxiety disorders. However, the underlying circuit and cellular mechanisms have remained elusive. Here we show that mice with Erbb4 gene deficiency in somatostatin-expressing (SOM+) neurons exhibit heightened anxiety as measured in the elevated plus maze test and the open field test, two assays commonly used to assess anxiety-related behaviors in rodents. Using a combination of electrophysiological, molecular, genetic and pharmacological techniques we demonstrate that the abnormal anxiety in the mutant mice is caused by enhanced excitatory synaptic inputs onto SOM+ neurons in the central amygdala (CeA), and the resulting reduction in inhibition onto downstream SOM+ neurons in the BNST. Notably, our results indicate that an increase in dynorphin signaling in SOM+ CeA neurons mediates the paradoxical reduction in inhibition onto SOM+ BNST neurons, and that the consequent enhanced activity of SOM+ BNST neurons is both necessary for and sufficient to drive the elevated anxiety. Finally, we show that the elevated anxiety and the associated synaptic dysfunctions and increased dynorphin signaling in the CeA-BNST circuit of the Erbb4 mutant mice can be recapitulated by stress in wild-type mice. Together, our results unravel previously unknown circuit and cellular processes in the central extended amygdala that can cause maladaptive anxiety.
2018-05-31 | GSE113979 | GEO