The influence of early life stress on social behavior and transcriptome in the prefrontal cortex.
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PROVIDER: PRJNA746344 | ENA |
REPOSITORIES: ENA
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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.
2021-11-30 | GSE180055 | GEO
Project description:Behavioral analysis confirmed that the 14-day social defeat sessions resulted in induction of depressive-like states measured in social interaction and light/dark tests. The combined data show that stress-induced depressive states are associated with molecular and structural changes that demyelinate the prefrontal cortex.
2017-06-12 | GSE84572 | GEO
Project description:Gene expression profiling was carried out on prefrontal cortex mRNA samples collected from 10 animals subject to repeated social threat (pooled into 2 groups of 5) and 10 animals subject to non-threatening control conditions (pooled into 2 groups of 5). The primary research question is whether gene expression differs in prefrontal cortex tissue from animals exposed to social threat vs non-threatening control conditions. Keywords: Risk prediction RNA from 5 mice/sample was pooled to generate 4 total samples: 2 from mice subject to repeated social threat, and 2 from control mice.
2010-04-12 | E-GEOD-16660 | biostudies-arrayexpress
Project description:The neurobiological origins of social behaviors are incompletely understood. Here we utilized synthetic biology approaches to reprogram the function of ZFP189, a transcription factor whose expression and function in rodent prefrontal cortex was previously demonstrated to be protective against stress-induced social deficits. We created novel synthetic ZFP189 transcription factors including ZFP189VPR, which activates the transcription of target genes and therefore exerts opposite functional control from the endogenous, transcriptionally repressive ZFP189WT. Following viral delivery of these synthetic ZFP189 transcription factors to mouse prefrontal cortex, we observe that ZFP189-mediated transcriptional control promotes mature dendritic spine morphology on transduced pyramidal neurons. Interestingly, inversion of ZFP189-mediated transcription in this brain area, achieved by viral delivery of synthetic ZFP189VPR, precipitates social behavioral deficits in terms of social interaction, motivation, and the cognition necessary for the maintenance of social hierarchy, without other observable behavioral deficits. RNA sequencing of virally manipulated prefrontal cortex tissues reveals that ZFP189 transcription factors of opposing regulatory function have opposite influence on the expression of genetic transposable elements as well as genes that participate in adaptive immune functions. Collectively, this work reveals that ZFP189 function in the prefrontal cortex coordinates structural and transcriptional neuroadaptations necessary for complex social behaviors, and does so by regulating transposable element-rich regions of DNA to control the expression of immune-related genes. Given the evidence for a co-evolution of social behavior and the brain immune response, we posit that ZFP189 may have evolved to augment brain transposon-associated immune function as a way of enhancing an animal’s capacity for functioning in social groups.
2024-02-09 | GSE246064 | GEO
Project description:Gene expression profiling was carried out on prefrontal cortex mRNA samples collected from 10 animals subject to repeated social threat (pooled into 2 groups of 5) and 10 animals subject to non-threatening control conditions (pooled into 2 groups of 5). The primary research question is whether gene expression differs in prefrontal cortex tissue from animals exposed to social threat vs non-threatening control conditions. Keywords: Risk prediction
2010-03-31 | GSE16660 | GEO
Project description:Autism spectrum disorder (ASD) is a heterogenous neurodevelopmental disorder with complex pathophysiology including both genetic and environmental factors. Recent evidence demonstrates the gut microbiome and its resultant metabolome can influence brain and behavior and have been implicated in ASD. To investigate gene by microbiome interactions in a model for genetic risk of ASD, we utilize mutant mice carrying a deletion of the ASD-associated Shank3 gene (Shank3KO). Shank3KO have altered microbiome composition and function at baseline in addition to social deficits. Further depletion of the microbiome with antibiotics exacerbates social deficits in Shank3KO, and results in transcriptional changes in the frontal cortex. Supplementation with the microbial metabolite acetate leads to reversal of social behavioral phenotypes even in mice with a depleted microbiome, and significantly alters transcriptional regulation in the prefrontal cortex. These results suggest a key role for the gut microbiome and the neuroactive metabolite acetate in regulating ASD-like behaviors.
2023-03-02 | GSE225983 | GEO
Project description:The medial prefrontal cortex (mPFC) is known as a hub of social hierarchy determination in the brain, Using high throughput single cell transcriptomic analysis and projection-specific genetic manipulation, we discovered that the expression level of Pou3f1 in mPFC-VTA neurons controls social hierarchy.
2023-12-11 | GSE222185 | GEO
Project description:Social behavioral changes are a hallmark of several neurodevelopmental and neuropsychiatric conditions, nevertheless the underlying neural substrates of such dysfunction remain poorly understood. Building evidence points to the prefrontal cortex (PFC) as one of the key brain regions that orchestrates social behavior. We used this concept with the aim to develop a translational rat model of social-circuit dysfunction, the chronic PFC activation model (CPA). Chemogenetic designer receptor hM3Dq was used to induce chronic activation of the PFC over 10 days, and the behavioral and electrophysiological signatures of prolonged PFC hyperactivity were evaluated. To test the sensitivity of this model to pharmacological interventions on longer timescales, and validate its translational potential, the rats were treated with our novel highly selective oxytocin receptor (OXTR) agonist RO6958375, which is not activating the related vasopressin V1a receptor. CPA rats showed reduced sociability in the three-chamber sociability test, and a concomitant decrease in neuronal excitability and synaptic transmission within the PFC as measured by electrophysiological recordings in acute slice preparation. Sub-chronic treatment with a low dose of the novel OXTR agonist following CPA interferes with the emergence of PFC circuit dysfunction, abnormal social behavior and specific transcriptomic changes. These results demonstrate that sustained PFC hyperactivity modifies circuit characteristics and social behaviors in ways that can be modulated by selective OXTR activation and that this model may be used to understand the circuit recruitment of prosocial therapies in drug discovery.
2023-11-05 | GSE246666 | GEO
Project description:Early-life stress has been linked to multiple neurodevelopmental and neuropsychiatric deficits. Our previous studies have linked maternal presence/absence from the nest in developing rat pups to changes in prefrontal cortex activity. Furthermore, we have shown that these changes are modulated by serotonergic signaling. Here we test whether changes in prefrontal cortex activity during early-life affect the developing cortex leading to behavioral alterations in the adult. We show that inhibiting the prefrontal cortex of mouse pups leads to cognitive deficits in the adult comparable to those seen following maternal separation. Moreover, we show that activating the prefrontal cortex during maternal separation can prevent these behavioral deficits. To test how maternal separation affects the transcriptional profile of the prefrontal cortex we performed single-nucleus RNA sequencing. Maternal separation lead to differential gene expression almost exclusively in inhibitory neurons. Among others, we found changes in GABAergic and serotonergic pathways in these interneurons. Interestingly, both maternal separation and early-life prefrontal cortex inhibition led to changes in physiological responses in prefrontal activity to GABAergic and serotonergic antagonists that were similar to the responses of more immature brains. Prefrontal activation during maternal separation prevented these changes. These data point to a crucial role of prefrontal cortex activity during early-life in behavioral expression in adulthood
2024-03-14 | GSE254342 | GEO
Project description:In order to better understand the effects of social stress on the prefrontal cortex, we investigated gene expression in mice subjected to acute and repeated social encounters of different duration using microarrays. The observed up-regulation of genes associated with vascular system and brain injury suggests that stressful social encounters may affect brain function through the stress-induced dysfunction of the vascular system. We studied gene expression profiles of prefrontal cortices of male mice subjected to social stress of different durations: Comparisons included: acute stress (24 hours after single social stress episode) vs. acute control (unstressed), stress-8 days vs. control-8 days, stress-13 days vs. control-13 days, stress-13 days+5 days of rest vs. control-13 days+5 days of rest. For each comparison, we analyzed 3 biological replicates per group. Two of out of three biological replicates were further replicated in dye swap (final dye swap failed due to problem during microarray hybridization). Each biological replicate consisted of equal amounts of total RNA from 3 mice subjected to the same experimental condition.
2015-01-07 | E-GEOD-64734 | biostudies-arrayexpress