Mus musculus
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PROVIDER: PRJNA102237 | ENA |
REPOSITORIES: ENA
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Project description:ATP-dependent chromatin remodeling proteins are being implicated increasingly in the regulation of complex behaviors, including models of several psychiatric disorders. Here, we demonstrate that Baz1b, an accessory subunit of the ISWI family of chromatin remodeling complexes, is upregulated in the nucleus accumbens (NAc), a key brain reward region, in both chronic cocaine-treated mice and mice that are resilient to chronic social defeat stress. In contrast, no regulation is seen in mice that are susceptible to this chronic stress. Viral-mediated overexpression of Baz1b, along with its associated subunit Smarca5, in mouse NAc is sufficient to potentiate both rewarding responses to cocaine, including cocaine self-administration, and resilience to chronic social defeat stress. However, despite these similar, proreward behavioral effects, genome-wide mapping of BAZ1B in NAc revealed mostly distinct subsets of genes regulated by these chromatin remodeling proteins after chronic exposure to either cocaine or social stress. Together, these findings suggest important roles for BAZ1B and its associated chromatin remodeling complexes in NAc in the regulation of reward behaviors to distinct emotional stimuli and highlight the stimulus-specific nature of the actions of these regulatory proteins. BAZ1B (WSTF) ChIP-seq of mouse. Cocaine vs Saline, 3 biological replicates. In social defeat model: Normal control vs Susceptible vs Resilient, 3 biological replicates.
2016-07-30 | E-GEOD-85005 | biostudies-arrayexpress
Project description:Stress is a major influence on mental health status; the ways that individuals respond to or copes with stressors determine whether they are negatively affected in the future. Stress responses are established by an interplay between genetics, environment, and life experiences. Psychosocial stress is particularly impactful during adolescence, a critical period for the development of mood disorders. In this study we compared two established, selectively-bred Sprague Dawley rat lines, the “internalizing” bred Low Responder (bLR) line versus the “externalizing” bred High Responder (bHR) line, to investigate how genetic temperament and adolescent environment impact future responses to social interactions and psychosocial stress, and how these determinants of stress response interact. Animals were exposed to social and environmental enrichment in adolescence prior to experiencing social defeat and were then assessed for social interaction and anxiety-like behavior. Adolescent enrichment caused bLR rats to display less social avoidance, more social interaction, less submission during defeat, and resilience to the prolonged effects of social stress on corticosterone, while enrichment caused bHR animals to show greater aggression during defeat and during a neutral social encounter, and decreased anxiety-like behavior. To gain insight into the development of social resilience in the anxious phenotype bLRs, RNA-seq was conducted on the hippocampus and nucleus accumbens, two brain regions that mediate stress regulation and social behavior. Gene sets previously associated with stress, social behavior, aggression and exploratory activity were enriched with differential expression in both regions, with a particularly large effect on gene sets that regulate social behaviors. These findings provide further evidence that adolescent enrichment can serve as an inoculating experience against future stressors. The ability to induce social resilience in a usually anxious line of animals by manipulating their environment has translational implications, as it underscores the feasibility of intervention strategies targeted at genetically vulnerable adolescent populations.
2024-05-01 | GSE237890 | GEO
Project description:We performed high-throughput profiling of gene expression in aPVT-projectors in the mPFC of DBA2/J mice subjected to subchronic and mild social defeat stress. DBA mice were subjected to 5-day of social defeat stress and then tested their social interaction and anhedonic state. After behavioral tests, mice were divided into five subtypes: SA, social interaction deficit, ANH: anhedonia, SA:ANH, both social dificit and anhedonia, RES, resilience and non-stressed (NS) control. Mice were euthanized for tissue collection. We then conducted the Immunoprecipitation and RNA-seq. Our study provided insights into the understanding of the molecular mechanisms underlying behavioral heterogeneity.
2024-01-15 | GSE238142 | GEO
Project description:Background: Examining transcriptional regulation by existing antidepressants in key neural circuits implicated in depression, and understanding the relationship to transcriptional mechanisms of susceptibility and natural resilience, may help in the search for new therapeutics. Further, given the heterogeneity of treatment response in human populations, examining both treatment response and non-response is critical. Methods: We compared the effects of a conventional monoamine-based tricyclic antidepressant, imipramine (14 daily injections), and a rapidly acting, experimental, non-monoamine-based antidepressant, ketamine (single injection), in mice subjected to chronic social defeat stress, a validated model of depression, and used RNA-sequencing to analyze transcriptional profiles associated with susceptibility, resilience and antidepressant response and non-response in prefrontal cortex (PFC), nucleus accumbens, hippocampus, and amygdala. Results: We identified approximately equal numbers of responder and non-responder mice following ketamine or imipramine treatment. Ketamine induced more expression changes in hippocampus than other brain regions; imipramine induced more expression changes in nucleus accumbens and amygdala. Transcriptional profiles in ketamine and imipramine responders were most similar in PFC, where the least transcriptional regulation occurred for each drug. Non-response reflected both the lack of response-associated gene expression changes and unique gene regulation. In responders, both drugs reversed susceptible associated transcriptional changes as well as induced resilient associated transcription in PFC, with effects varying by drug and brain region studied. Conclusions: We generated a uniquely large resource of gene expression data in four inter-connected limbic brain regions implicated in depression and its treatment with imipramine or ketamine. Our analyses highlight the PFC as a key site of common transcriptional regulation by both antidepressant drugs and in both reversing susceptibility and inducing resilience associated molecular adaptations. In addition, we found region-specific effects of each drug suggesting both common and unique effects of imipramine versus ketamine. mRNA profiles of susceptibility to chronic social defeat stress as well as treatment response were generated across 4 separate brain regions, with a sample size of 3-5 per group.
2016-07-27 | E-GEOD-81672 | biostudies-arrayexpress
Project description:Susceptibility to depression-like behavioral abnormalities in mice is studied with a well-established social defeat stress model. Responses to social defeat are associated with widespread transcriptomic changes in several brain regions. Here we present the first study of genome-wide cytosine methylation patterns of mice susceptible to social defeat stress using whole-genome bisulfite sequencing on DNA from the nucleus accumbens, a key brain reward region implicated in depression. We find a greater proportion of CpG hypermethylation than hypomethylation in susceptible mice compared to controls, with an opposite trend in the CHG and CHH contexts. Among the genes with the largest extent of differential methylation we find several which have been identified in earlier studies of gene expression changes related to social defeat, including estrogen receptor alpha (encoded by Esr1) and the deleted in colorectal cancer (Dcc) gene. Genes exhibiting differential methylation are enriched in GO terms of nervous system development, neurogenesis and structure development, which associated with learning memory and stress response. Our data provide a new evidence of the association of DNA methylation profiles and susceptibility to chronic stress.
2019-03-16 | GSE126955 | GEO
Project description:While stressful life events are an important cause of psychopathology such as Post-Traumatic Stress Disorder (PTSD) and Major Depressive Disorder (MDD), most individuals exposed to chronic stress remain psychologically unperturbed. The molecular mechanisms such variations in stress resilience remain to be explored. Utilizing a mouse social defeat paradigm as a model for chronic social stress exposure, we segregated socially defeated c57bl/6J mice into Susceptible and Unsusceptible groups based on scores of social avoidance, and these groups differ along multiple behavioral and physiological domains. To explore neuroplastic changes within the mesolimbic dopamine circuit that may explain variations in susceptibility, we examined global patterns of gene expression within the VTA (ventral tegmental area) and the NAc (nucleus accumbens). Tissue punches of NAc and VTA were obtained from either non-defeated control, Susceptible and Unsusceptible mice approximately 48 hours after the cessation of social defeat stress. Data from Illumina sentrix gene expression microarrays revealed three main findings: (1) the total number of genes significantly up or downregulated was considerably higher within the NAc, (2) the Unsusceptible phenotype was associated with the regulation of a much higher number of genes, and (3) as compared to the NAc, the VTA displayed far fewer genes that were identically regulated in both Susceptible and Unsusceptible groups. Taken together, these data strongly suggest that the VTA is an important substrate for transcriptional changes that can be correlated with variations in Susceptibility. In addition, they suggest that changes in anxiety (found in both Susceptible and Unsusceptible groups) versus changes in reward behavior (found only in Susceptilbe mice) can be explained by gene expression changes within the mesolimbic dopamine circuit. Keywords: neural stress response
2007-09-01 | GSE8870 | GEO
Project description:Introgressed variants from other species can be an important source of genetic variation because they may arise rapidly, can include multiple mutations on a single haplotype, and have often been pretested by selection in the species of origin. Although introgressed alleles are generally deleterious, several studies have reported introgression as the source of adaptive alleles-including the rodenticide-resistant variant of Vkorc1 that introgressed from Mus spretus into European populations of Mus musculus domesticus. Here, we conducted bidirectional genome scans to characterize introgressed regions into one wild population of M. spretus from Spain and three wild populations of M. m. domesticus from France, Germany, and Iran. Despite the fact that these species show considerable intrinsic postzygotic reproductive isolation, introgression was observed in all individuals, including in the M. musculus reference genome (GRCm38). Mus spretus individuals had a greater proportion of introgression compared with M. m. domesticus, and within M. m. domesticus, the proportion of introgression decreased with geographic distance from the area of sympatry. Introgression was observed on all autosomes for both species, but not on the X-chromosome in M. m. domesticus, consistent with known X-linked hybrid sterility and inviability genes that have been mapped to the M. spretus X-chromosome. Tract lengths were generally short with a few outliers of up to 2.7 Mb. Interestingly, the longest introgressed tracts were in olfactory receptor regions, and introgressed tracts were significantly enriched for olfactory receptor genes in both species, suggesting that introgression may be a source of functional novelty even between species with high barriers to gene flow.
| S-EPMC8784167 | biostudies-literature
Project description:Chronic social defeat (CSD) in mice has been increasingly employed in experimental resilience research. Particularly, the degree of CSD-induced social avoidance is used to classify animals into resilient (socially non-avoidant) versus susceptible (avoidant). Inspired by human data pointing to threat-safety discrimination and responsiveness to extinction training of aversive memories as characteristics of resilient individuals, we here describe a translationally informed stratification which identified three phenotypic subgroups of mice following CSD: the Discriminating-avoiders, characterised by successful social threat-safety discrimination and successful extinction of social avoidance; the Indiscriminate-avoiders, showing fear generalisation, and the Non-avoiders (absence of social avoidance) displaying impaired conditioned learning. Furthermore, and supporting the biological validity of our approach, we uncovered subgroup-specific transcriptional signatures in classical fear conditioning and anxiety-related brain regions. Our reconceptualisation of resilience in mice refines the currently used dichotomous classification and contributes to advancing future translational approaches.
2023-02-28 | GSE161726 | GEO
Project description:Differential gene expression in peripheral blood leukocytes from mice subject to repeated social defeat
| PRJNA204591 | ENA