Project description:This study aimed to investigate the effects of depression on transcriptome in ileum using a subchronic and mild social defeat stress (sCSDS) model. In addition to exhibiting social deficit and hyperphagia-like behavior, the sCSDS mice keep much more water in their body than control mice. In order to investigate the effect of social defeat stress on not only central nervous system but also function of gastrointestinal tract, the gene expression in ileum of stressed mice was compared with control mice. We used microarrays to detail the gene expression after 10 days of social defeat stress and identified distinct classes of down-regulated genes during this process.
Project description:This study aimed to investigate the effects of depression on transcriptome in ileum using a subchronic and mild social defeat stress (sCSDS) model. In addition to exhibiting social deficit and hyperphagia-like behavior, the sCSDS mice keep much more water in their body than control mice. In order to investigate the effect of social defeat stress on not only central nervous system but also function of gastrointestinal tract, the gene expression in ileum of stressed mice was compared with control mice. We used microarrays to detail the gene expression after 10 days of social defeat stress and identified distinct classes of down-regulated genes during this process. The duration of physical contacts was set at 5 min after the first attack bite at Day 1, and then was reduced 0.5 min per day from Day 2 to Day 10.
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.
Project description:We performed high-throughput profiling of gene expression in the mPFC of stress-vulnerable DBA2/J mice subjected to subchronic and mild social defeat stress.DBA mice were subjected to 5-day of social defeat stress and then injected with KDM5C inhibitor (KDM5Ci) or vehicle. After behavioral tests, mice were euthanized for tissue collection. We then conducted the transcriptomics analysis. Our study provided insights into the understanding of the molecular mechanisms underlying stress susceptibility and provide the role of KDM5C in stress-induced behavioral changes.
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.
Project description:We performed high-throughput profiling of gene expression in the anterior cingulate cortex of stress-vulnerable BALB/c mice subjected to social defeat stress. BALB/c mice were subjected to 5-day of social defeat stress and euthanized for tissue collection. We then conducted the transcriptomics analysis. Our study provided insights into the understanding of the molecular mechanisms underlying the behavioral response to stress.
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.