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Expression (Gene) in the endothelial cells of the mouse male prefrontal cortex (PFC) following 10-day chronic social stress exposure [male CSDS]

ABSTRACT: Cell-specific transcriptomic analysis were performed on PFC endothelial cells of unstressed controls (CTRL), stress-susceptible (SS) and resilient (RES) mice to identify novel genes and pathways involved in stress responses

ORGANISM(S): Mus musculus

PROVIDER: GSE182671 | GEO | 2021/10/29

REPOSITORIES: GEO

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Expression (Gene) in the endothelial cells of the mouse female prefrontal cortex (PFC) following 10-day chronic social stress exposure [Female_CSDS]

Project description:Cell-specific transcriptomic analysis were performed on PFC endothelial cells of unstressed controls (CTRL), stress-susceptible (SS) and resilient (RES) mice to identify novel genes and pathways involved in stress responses

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Expression (Gene) in the endothelial cells of the mouse female prefrontal cortex (PFC) following 10-day chronic social stress or 6-day subchronic variable stress exposure [Female_CSDS_vs_SCVS]

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Expression (Gene) in the endothelial cells of the mouse female prefrontal cortex (PFC) following 10-day chronic social stress or 6-day subchronic variable stress exposure was compared to male [Male_SS_vs_Female_SS_or_SCVS]

Project description:Cell-specific transcriptomic analysis were performed on PFC endothelial cells of stress-susceptible (SS) and resilient (RES) mice along with females subjected to 6 days of subchronic variable stress to identify novel genes and pathways involved in stress responses. These gene lists were compared to published findings obtained in the male NAc following 10 days of chronic social stress exposure (Dudek et al., 2020)

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Expression (Gene) in the endothelial cells of the mouse female prefrontal cortex (PFC) following 6-day subchronic variable stress (SCVS) exposure [Female_SCVS]

Project description:Cell-specific transcriptomic analysis were performed on PFC endothelial cells of unstressed controls (CTRL) and mice exposed to SCVS to identify novel genes and pathways involved in stress responses

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Zfp189 Mediates Stress Resilience Through a CREB-Regulated Transcriptional Network in Prefrontal Cortex

Project description:Stress resilience involves numerous brain-wide transcriptional changes. Determining the organization and orchestration of these transcriptional events may reveal novel antidepressant targets, but this remains unexplored. Here, we characterize the resilient transcriptome with co-expression analysis and identify a single transcriptionally-active uniquely-resilient gene network. Zfp189, a previously unstudied zinc finger protein, is the top network key driver and its overexpression in prefrontal cortical (PFC) neurons preferentially activates this network, alters neuronal activity and promotes behavioral resilience. CREB, which binds Zfp189, is the top upstream regulator of this network. To probe CREB-Zfp189 interactions as a network regulatory mechanism, we employ CRISPR-mediated locus-specific transcriptional reprogramming to direct CREB selectively to the Zfp189 promoter. This single molecular interaction in PFC neurons recapitulates the pro-resilient Zfp189-dependent downstream effects on gene network activity, electrophysiology and behavior. These findings reveal an essential role for Zfp189 and a CREB-Zfp189 regulatory axis in mediating a central transcriptional network of resilience.

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The influence of early life stress on social behavior and transcriptome in the prefrontal cortex.

Project description:Early life stress (ELS), such as neglect and maltreatment, exhibits a strong impact on the mental and brain development of children. However, it is not fully understood how ELS affects the function in developing prefrontal cortex (PFC). In this study, we performed social isolation on weaned pre-adolescent mice and investigated how ELS could affect the function in behavior and transcriptome in PFC. We found that reductions of social interaction, social preference, and social novelty in ELS mice. Moreover, an increase of anxiety-like behavior was observed in ELS mice, but there were no changes in weight and repetitive behavior. To identify the gene involved in social behavior, we conducted transcriptome analysis and identified 15 differentially expressed genes (DEGs) in the PFC of ELS mice. These genes were involved in transcriptional regulation, stress, and synaptic signaling. We also found that a decreased number of neurons and an increased number of microglia in the PFC of ELS mice. These results suggest that ELS affects PFC cytoarchitecture by stress signal transduction and eventually alters mouse behavior. Our study demonstrates that ELS influences behavior, transcriptome and cytoarchitecture in the brain of adolescent mice.

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Prefrontal cortical synaptoproteome profile combined with machine learning predict resilience towards chronic social isolation in rats

Project description:Chronic social isolation (CSIS), an animal model of depression, generates two stress-response phenotypes: CSIS-resilient and CSIS-susceptible. However, the molecular mechanism underlying resilience to CSIS remains unclear. We aimed to investigate the prefrontal cortical synaptoproteome profile between CSIS-resilient, CSIS-susceptible and control rats in order to identify predictive proteins for the resilience phenotype. Comparison of CSIS-resilient versus CSIS-susceptible rats revealed downregulated glycolysis intermediate Aldoc and upregulated Cltc, Cam2a, Syn and Fasn proteins involved in neuronal transmission, synaptic vesicle trafficking and fatty acid synthesis. Comparison of CSIS-resilient and control rats revealed downregulated mitochondrial proteins Atp5f1b and Cs, and upregulated Prkcg, Slc17a7, and Sv2a proteins involved in signal transduction and synaptic trafficking. These proteins make the animal groups linearly separable, and 100% validation accuracy is achieved by standard machine learning models. In addition, we identified the most significant proteins for discriminating CSIS-resilient vs. CSIS-susceptible or control rats by using Support Vector Machine with greedy forward search and Random Forest, resulting in four panels of discriminative proteins. Proteomics-data-driven machine learning algorithms can provide a platform for accessing predictive features and provide additional insight into the molecular mechanisms of synaptic neurotransmission involved in stress resilience.

2024-04-23 | PXD047159 | Pride

Expression (Gene) in the endothelial cells of the mouse male prefrontal cortex (PFC) following 10-day chronic social stress exposure [male CSDS]

Project description:Expression (Gene) in the endothelial cells of the mouse male prefrontal cortex (PFC) following 10-day chronic social stress exposure [male CSDS]

| PRJNA757402 | ENA

Medial prefrontal cortex transcriptome of mice susceptible or resilient to chronic stress

Project description:Stressful circumstances are significant contributors to mental illnesses, such as major depressive disorder. Anhedonia, which is the loss of the ability to enjoy pleasure, including rewarding activities or social contexts, is considered a key symptom of depression. Although stress-induced depression is associated with anhedonia in humans and animals, the underlying molecular mechanisms of anhedonic responses remain poorly understood. In this study, we conducted RNA sequencing to profile the medial prefrontal cortex which was substantially associated with the CUS-induced anhedonic behavioral phenotypes. Employing chronic unpredictable stress (CUS), we determined two subpopulations based on sucrose preference, which was highly correlated with social reward: susceptible (SUS, anhedonic) vs. resilient (RES, non-anhedonic) groups. We identified Syt4 as a hub gene in a gene network unique to anhedonia by conducting a weighted gene co-expression network analysis of the RNA sequencing data from the mPFC of SUS and RES mice. We also confirmed that Syt4 overexpression in the mPFC was pro-susceptible, while the Syt4 knockdown was pro-resilient; the pro-susceptible effects of SYT4 were mediated through the reduction of brain-derived neurotrophic factor (BDNF)-tropomyosin receptor kinase B (TrkB) signaling in the mPFC. These findings suggested that SYT4-BDNF interactions in the mPFC could be a crucial regulatory mechanism of anhedonic susceptibility to chronic stress.

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Prefrontal cortex cytoplasmic proteome and machine learning-based predictors of resilience towards chronic social isolation in rats

Project description:Chronic social isolation (CSIS) generates two stress-related phenotypes, resilience and susceptibility. Although brain energy metabolism is important in regulating social behaviors, the molecular mechanisms underlying CSIS resilience remain unclear. To identify protein changes and altered biochemical pathways and processes for resilience to CSIS, prefrontal cortical cytosolic proteomic profiling was performed comparing CSIS-resilient with CSIS-susceptible and control rats. Potential predictive proteins discriminating between the CSIS-resilient and CSIS-susceptible groups were identified by support vector machine-based sequential feature selection and random forest-based feature importance scores. Predominantly decreased levels of glycolytic enzymes, G protein-coupled receptor proteins, Ras subfamily of GTPase proteins, and antioxidant proteins were found in CSIS-resilient vs. CSIS-susceptible groups. Altered levels of Gapdh and proteins involved in microtubule and cytoskeletal organization, and calcium-binding proteins were identified between the two phenotypes. These dynamic changes were accompanied by increased levels of proteins involved in GABA synthesis, the proteasome system, nitrogen metabolism, and chaperone-mediated protein folding. The overall ratio of significantly up- and down-regulated cytosolic proteins suggests adaptive cellular alterations as part of the stress-coping process specific for the CSIS-resilient phenotype.

2024-04-23 | PXD048641 | Pride

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