Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

DNA Methyltransferase 3A Mediates the Sustained Effects of Stress on Synaptic Functions and Behaviors [RNA-seq]

ABSTRACT: Emerging evidence suggests that epigenetic mechanisms regulate aberrant gene transcription in stress-associated mental disorders. However, it remains to be elucidated about the role of DNA methylation and its catalyzing enzymes, DNA methyltransferases (DNMTs), in this process. Here we found that rats exposed to chronic (2-week) unpredictable stress exhibited a substantial reduction of Dnmt3a after stress cessation in the prefrontal cortex (PFC), a key target region of stress. Treatment of unstressed control rats with DNMT inhibitors recapitulated the effect of chronic unpredictable stress on decreased AMPAR expression and function in PFC. In contrast, overexpression of Dnmt3a in PFC of stressed animals prevented the loss of glutamatergic responses. Moreover, the stress-induced behavioral abnormalities, including the impaired recognition memory and aggressive behaviors, were ameliorated by Dnmt3a expression in PFC of stressed animals. Lastly, we found genome-wide DNA methylation changes in PFC of stressed rats are selectively enriched at several pathways, such as axon guidance, Wnt signaling and neurotransmission. These findings have therefore recognized the role of DNA epigenetic modification in stress-induced disturbance of synaptic functions and cognitive & emotional processes.

ORGANISM(S): Rattus norvegicus

PROVIDER: GSE147845 | GEO | 2020/12/31

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

DNA Methyltransferase 3A Mediates the Sustained Effects of Stress on Synaptic Functions and Behaviors [RRBS]

Project description:Emerging evidence suggests that epigenetic mechanisms regulate aberrant gene transcription in stress-associated mental disorders. However, it remains to be elucidated about the role of DNA methylation and its catalyzing enzymes, DNA methyltransferases (DNMTs), in this process. Here we found that rats exposed to chronic (2-week) unpredictable stress exhibited a substantial reduction of Dnmt3a after stress cessation in the prefrontal cortex (PFC), a key target region of stress. Treatment of unstressed control rats with DNMT inhibitors recapitulated the effect of chronic unpredictable stress on decreased AMPAR expression and function in PFC. In contrast, overexpression of Dnmt3a in PFC of stressed animals prevented the loss of glutamatergic responses. Moreover, the stress-induced behavioral abnormalities, including the impaired recognition memory and aggressive behaviors, were ameliorated by Dnmt3a expression in PFC of stressed animals. Lastly, we found genome-wide DNA methylation changes in PFC of stressed rats are selectively enriched at several pathways, such as axon guidance, Wnt signaling and neurotransmission. These findings have therefore recognized the role of DNA epigenetic modification in stress-induced disturbance of synaptic functions and cognitive & emotional processes.

2020-12-31 | GSE147846 | GEO

Chronic Psychological Stress regulates Visceral Adipocyte-mediated Glucose Metabolism and Inflammatory Circuits in male Rats

Project description:In this study we employed the chronic unpredictable stress (CUS) rat model that leads to anxiety features comparable to humans and validated in several published reports as a well-characterized model of depression symptoms with high predictive validity. Cytokines and activated intracellular kinase levels were determined using high throughput multiplex assays. RNA from freshly isolated adipocytes was used to run whole genome expression microarray profiling in control and stressed rats. Adipocyte function was assessed via tritiated glucose uptake assay. The expression of four cytokines (TNFÎ±, IL-1Î², IL-6 and MCP-1) was validated via real-time PCR and the all showed increased expression levels with chronic unpredictable stress. Male rats were subjected to chronic unpredictable stress for 35 days and total body fat was measured. The analyses presented here represents data from experiments performed in 6 control and 6 stressed rats in parallel. All cells for RNA isolation were collected at the conclusion of the 35 day stress protocol.

2014-06-03 | E-GEOD-47754 | biostudies-arrayexpress

Chronic Psychological Stress regulates Visceral Adipocyte-mediated Glucose Metabolism and Inflammatory Circuits in male Rats

Project description:In this study we employed the chronic unpredictable stress (CUS) rat model that leads to anxiety features comparable to humans and validated in several published reports as a well-characterized model of depression symptoms with high predictive validity. Cytokines and activated intracellular kinase levels were determined using high throughput multiplex assays. RNA from freshly isolated adipocytes was used to run whole genome expression microarray profiling in control and stressed rats. Adipocyte function was assessed via tritiated glucose uptake assay. The expression of four cytokines (TNFα, IL-1β, IL-6 and MCP-1) was validated via real-time PCR and the all showed increased expression levels with chronic unpredictable stress.

2014-06-03 | GSE47754 | GEO

Chronic mild stress and Lactobacillus experiments on mice

Project description:Mice were devided into three groups (Naive untreated, Stressed untreated, Stressed + Lacto). The stressed groups were subjected to unpredictable chronic mild stress for seven weeks. Three weeks into the protocol, the +Lacto groups were administered probiotic Lactobacillus daily.

2014-10-28 | ST000296 | MetabolomicsWorkbench

Brain-Immune system-Gut Interaction in Chronic Mild Stress (CMS +/- Lacto)

2017-06-19 | ST000696 | MetabolomicsWorkbench

Molecular and Cellular Mechanisms for Differential Effects of Chronic Social Isolation Stress in Males and Females

Project description:Chronic social isolation stress during adolescence induces susceptibility for neuropsychiatric disorders. Here we show that 5-week post-weaning isolation stress induces sex-specific behavioral abnormalities and neuronal activity changes in the prefrontal cortex (PFC), basal lateral amygdala (BLA), and ventral tegmental area (VTA). Chemogenetic manipulation, optogenetic recording, and in vivo calcium imaging identify that the PFC to BLA pathway is causally linked to heightened aggression in stressed males, and the PFC to VTA pathway is causally linked to social withdrawal in stressed females. Isolation stress induces genome-wide transcriptional alterations in a region-specific manner. Particularly, the upregulated genes in BLA of stressed males are under the control of activated transcription factor CREB, and CREB inhibition in BLA normalizes gene expression and reverses aggressive behaviors. On the other hand, neuropeptide Hcrt (Hypocretin/Orexin) is among the top-ranking downregulated genes in VTA of stressed females, and Orexin-A treatment rescues social withdrawal. These results have revealed molecular mechanisms and potential therapeutic targets for stress-related mental illness.

2022-03-22 | GSE198725 | GEO

Sex Differences in Nucleus Accumbens Transcriptome Profiles Associated with Susceptibility versus Resilience to Subchronic Variable Stress

Project description:Depression and anxiety disorders are more prevalent in females, but the majority of research in animal models, the first step in finding new treatments, has focused predominantly on males. Here we report that exposure to subchronic variable stress (SCVS) induces depression-associated behaviors in female mice, whereas males are resilient as they do not develop these behavioral abnormalities. In concert with these different behavioral responses, transcriptional analysis of nucleus accumbens (NAc), a major brain reward region, by use of RNA sequencing (RNA-seq) revealed markedly different patterns of stress regulation of gene expression between the sexes. Among the genes displaying sex differences was DNA methyltransferase 3a (Dnmt3a), which shows a greater induction in females after SCVS. Interestingly, Dnmt3a expression levels were increased in the NAc of depressed humans, an effect seen in both males and females. Local overexpression of Dnmt3a in NAc rendered male mice more susceptible to SCVS, whereas Dnmt3a knock-out in this region rendered females more resilient, directly implicating this gene in stress responses. Associated with this enhanced resilience of female mice upon NAc knock-out of Dnmt3a was a partial shift of the NAc female transcriptome toward the male pattern after SCVS. These data indicate that males and females undergo different patterns of transcriptional regulation in response to stress and that a DNA methyltransferase in NAc contributes to sex differences in stress vulnerability. mRNA profiles of sex-specific in stress response were generated in the Nucleus Accumbens for 3 female control mice, 3 male control mice, 3 stressed female mice, 3 stressed male mice. Cre-mediated Dnmt3a knock-out was performed on stressed mice, with 3 males and 3 females expressing control GFP and 3 males and 3 females expressing CRE/GFP.

2016-08-04 | E-GEOD-85136 | biostudies-arrayexpress

Early life stress in fathers impairs synaptic plasticity in the offspring - brain collected after acute swim stress

Project description:We show that traumatic stress experienced by males in early postnatal life impairs memory in their offspring, blocks long-term potentiation (LTP) and favors long-term depression (LTD). These effects are accompanied by suppression of key molecular pathways involved in neuronal plasticity both at rest and after acute stress. Male mice were exposed to chronic traumatic stress in early postnatal life and were later bred to naM-CM-/ve females to produce second-generation offspring. Memory performance was evaluated in the offspring, and synaptic plasticity was examined in the hippocampus and the amygdala, brain areas important for memory formation. The two groups tested were 1: offspring of fathers which were stressed (MSUS - maternal separation unpredictable stress) and 2: offspring of non-stressed fathers (control). Genome-wide gene expression in hippocampus of these two groups was assessed at rest and after acute stress (this study).

2014-07-01 | E-GEOD-47847 | biostudies-arrayexpress

Early life stress in fathers impairs synaptic plasticity in the offspring - brain collected at rest

2014-07-01 | E-GEOD-47846 | biostudies-arrayexpress