Mus musculus
Ontology highlight
ABSTRACT:
OTHER RELATED OMICS DATASETS IN: PXD006781
PROVIDER: PRJNA391140 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR5715030.fastq.gz | Fastqsanger.gz | |||
| SRR5715040.fastq.gz | Fastqsanger.gz | |||
| SRR5715050.fastq.gz | Fastqsanger.gz | |||
| SRR5715060.fastq.gz | Fastqsanger.gz | |||
| SRR5715070.fastq.gz | Fastqsanger.gz |
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Project description:Purpose: The goal of this study was to characterize molecular stress responses on transcriptional level in dorsal and ventral hippocampus separately. Methods: mRNA profiles of whole, dorsal and ventral hippocampus of mice 45min after first exposure to different acute stressors. The stressors were novelty (6min novel environment), restraint (30min immobilization), or cold swim (6min in 18 degree Celcius water). 5 mice were used per condition, using Illumina HiSeq4000. The sequence reads that passed quality filters were mapped with STAR, counted with RSEM and differential gene expression was calculated using the bioconducter package edgeR. Results: With our workflow, we identified 13902 genes per sample. Approximately 20% of the genes were differentially expressed between dorsal and ventral hippocampus at baseline, with a log2 fold change >±0.3 and p value <0.005. Approximately 100 genes are differentially expressed upon stress treatment in the whole hippocampus. If ventral and dorsal hippocampus were analyzed separately, numbers increased to 150 and 250 respectively. Stress-responsive genes vary between dorsal and ventral hippocampus, and also vary between different stressors. Further analysis identified a functional epigenetic gene cluster specific for the stress response in the ventral hippocampus. Conclusions: Our study represents the first RNA-seq analysis of dorsal and ventral hippocampus after different acute stress exposures.
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Project description:The hippocampus - one of the most studied brain regions – is a key target of the stress response and vulnerable to the detrimental effects of stress. Although its intrinsic organization is highly conserved throughout its long dorsal-ventral axis, the dorsal hippocampus is linked to spatial navigation and memory formation, whereas the ventral hippocampus is linked to emotional regulation. Here, we provide the first combined transcriptomic and proteomic profiling that reveals striking differences between dorsal and ventral hippocampus. Using various acute stress challenges we demonstrate that both regions display very distinct molecular responses, and that the ventral hippocampus is particularly responsive to the effects of stress. We demonstrate that separately analyzing dorsal and ventral hippocampus greatly increases the ability to detect region-specific stress effects, and we identify an epigenetic network, which is specifically sensitive to acute stress in the ventral hippocampus.
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Project description:Using NGS, we report the impact of chronic stress on the transcriptome of the dorsal and ventral hippocampus in the ewe. This study identifies specific transcriptional signatures of the dorsal VS ventral hippocampus (>220 DEG) and demonstrates a very limited transcriptional impact of stress, exclusively restricted to the dorsal hippocampus (<10 DEG).
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Project description:Dorsal and ventral parts of the hippocampus despite similar histological structure are known to be involved in performance of different functions. Previous studies using next generation sequencing showed that these two hippocampal parts differ in the expression of many genes, however, stability of dorsoventral gradient of gene expression remains open question. Here, we analyzed differential expression of genes between the dorsal and ventral hippocampus of rats in polyA-enriched samples and samples subjected to depletion of ribosomal RNA. We present here a detailed analysis of differentially expressed genes between the dorsal and ventral parts of the hippocampus. Intersection of our dataset with data of previous RNAseq studies revealed 544 genes are stably differentially expressed between the hippocampal parts suggesting that, despite strongly variability between the animals and sequencing approaches, there is a subset of genes whose expression stably differs between the dorsal and ventral hippocampus. Analysis of differential splicing showed that the dorsal and ventral parts of the hippocampus express 64 genes whose splice isoforms are different between the hippocampal parts. Furthermore, we show that depletion of ribosomal RNA increases representation of transposable elements in the RNAseq libraries and helps to detect a weak predominance of expression of these elements in the ventral hippocampus.
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Project description:The role of the hippocampus in learning and memory has been widely studied. However, studies of differences along the longitudinal axis indicate that the hippocampus is perhaps not a singular structure, but instead it is thought that the dorsal and ventral poles of the hippocampus have functional differences. An anatomical gradient of hippocampal inputs along the dorsal-ventral axis supports this notion. It has been recently shown that there is transcriptional differentiation along the longitudinal axis of the adult hippocampus, coinciding with functional and anatomical gradients. Understanding the development of the dorsal-ventral hippocampal axis will further our understanding of the different hippocmapal functional contributions along the longitudinal axis. However, analysis of transcriptional gradients along the dorsal ventral axis have not been studied in the neonatal rat during development. We performed an extensive bead-chip based geneome-wide analysis of transcriptional differences in dorsal, intermediate, and ventral hippocampal tissue of rats aged postnatal day 0 (P0), P9, P18 and P60.
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Project description:Engrams are considered to be substrates for memory storage, and the functional dysregulation of the engrams leads to cognition impairment.However, the cellular basis for these maladaptive changes lead to the forgetting of memories remains unclear. Here we found that the expression of autophagy protein 7 (Atg7) mRNA was dramatically upregulated in aged DG engrams, and led to the forgetting of contextual fear memory and the activation of surrounding microglia.To determine mechanism by which autophagy in DG engrams activates the surrounding microglia, mice were co-injected AAV-RAM-Cre either with AAV-Dio-Atg7-Flag or AAV-Dio- EYFP in dorsal dentate gyrus to overexpress ATG7 in the DG memory engrams. Microglia were separated using magnetic-activated cell sorting and subjected to RNA-Seq in dorsal hippocampus .Bioinformatics analysis shown overexpression of Atg7 in dorsal DG memory engrams caused an increase in the expression of Tlr2 in the surrounding microglia.Depletion of Toll-like receptor 2/4 (TLR2/4) in DG microglia prohibited excessive microglial activation and synapse elimination induced by the overexpression of ATG7 in DG engrams, and thus prevented forgetting. Furthermore, the expression of Rac1, a Rho-GTPases which regulates active forgetting in both fly and mice, was upregulated in aged engrams. Optogentic activation of Rac1 in DG engrams promoted the autophagy of the engrams, the activation of microglia, and the forgetting of fear memory. Invention of the Atg7 expression and microglia activation attenuated forgetting induced by activation of Rac1 in DG engrams. Together, our findings revealed autophagy-dependent synapse elimination of DG engrams by microglia as a novel forgetting mechanism.
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Project description:Here, we extensively characterize noradrenaline (NA) mediated transcriptomic response during acute stress in the mouse hippocampus. Combining for the first time bulk mRNA-sequencing and selective pharmacological manipulations of the NA system. We show that the NA mediates robust stress associated transcriptomic alterations across the dorsal and ventral hippocampus via β-adrenergic receptors
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