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Distinct molecular mechanisms of stress habituation in the mouse hippocampus

ABSTRACT: Distinct molecular mechanisms of stress habituation in the mouse hippocampus

PROVIDER: PRJNA1237711 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR32752300_1.fastq.gz	Fastqsanger.gz
	SRR32752300_2.fastq.gz	Fastqsanger.gz
	SRR32753800_1.fastq.gz	Fastqsanger.gz
	SRR32753800_2.fastq.gz	Fastqsanger.gz
	SRR32754400_1.fastq.gz	Fastqsanger.gz

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Distinct molecular mechanisms of stress habituation in the mouse hippocampus

Project description:We explore how the tightly regulated molecular response triggered by acute restraint stress becomes altered after repeated restraint exposure. Transcriptomic sampling of the mouse hippocampus at multiple time points revealed that repeated stress leads to widespread habituation, damping stress-induced gene expression of all stress-responsive genes. However, we find no evidence for the emergence of new response profiles or alterations in baseline gene expression. Using single-cell multi-omics, we show that these findings hold true across cell types, and we reveal cell type specific patterns of habituation. Transcriptomic and chromatin accessibility profiles identify two distinct mechanisms that contribute to the observed habituation patterns: an early cAMP-associated mechanism that is related to blunted transcription after chronic stress, and a late corticosterone-dependent mechanism that is linked to a shortened transcriptional response.

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Distinct transcriptomic, proteomic and epigenetic stress-responses in dorsal and ventral hippocampus

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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