Header

UZH-Logo

Maintenance Infos

Distinct Proteomic, Transcriptomic, and Epigenetic Stress Responses in Dorsal and Ventral Hippocampus


Floriou-Servou, Amalia; von Ziegler, Lukas; Stalder, Luzia; Sturman, Oliver; Privitera, Mattia; Rassi, Anahita; Cremonesi, Alessio; Thöny, Beat; Bohacek, Johannes (2018). Distinct Proteomic, Transcriptomic, and Epigenetic Stress Responses in Dorsal and Ventral Hippocampus. Biological Psychiatry, 84(7):531-541.

Abstract

BACKGROUND Acutely stressful experiences can trigger neuropsychiatric disorders and impair cognitive processes by altering hippocampal function. Although the intrinsic organization of the hippocampus is highly conserved throughout its long dorsal-ventral axis, the dorsal (anterior) hippocampus mediates spatial navigation and memory formation, whereas the ventral (posterior) hippocampus is involved in emotion regulation. To understand the molecular consequences of stress, detailed genome-wide screens are necessary and need to distinguish between dorsal and ventral hippocampal regions. While transcriptomic screens have become a mainstay in basic and clinical research, proteomic methods are rapidly evolving and hold even greater promise to reveal biologically and clinically relevant biomarkers. METHODS Here, we provide the first combined transcriptomic (RNA sequencing) and proteomic (sequential window acquisition of all theoretical mass spectra [SWATH-MS]) profiling of dorsal and ventral hippocampus in mice. We used three different acute stressors (novelty, swim, and restraint) to assess the impact of stress on both regions. RESULTS We demonstrated that both hippocampal regions display radically distinct molecular responses and that the ventral hippocampus is particularly sensitive to the effects of stress. Separately analyzing these structures greatly increased the sensitivity to detect stress-induced changes. For example, protein interaction cluster analyses revealed a stress-responsive epigenetic network around histone demethylase Kdm6b restricted to the ventral hippocampus, and acute stress reduced methylation of its enzymatic target H3K27me3. Selective Kdm6b knockdown in the ventral hippocampus led to behavioral hyperactivity/hyperresponsiveness. CONCLUSIONS These findings underscore the importance of considering dorsal and ventral hippocampus separately when conducting high-throughput molecular analyses, which has important implications for fundamental research as well as clinical studies.

Abstract

BACKGROUND Acutely stressful experiences can trigger neuropsychiatric disorders and impair cognitive processes by altering hippocampal function. Although the intrinsic organization of the hippocampus is highly conserved throughout its long dorsal-ventral axis, the dorsal (anterior) hippocampus mediates spatial navigation and memory formation, whereas the ventral (posterior) hippocampus is involved in emotion regulation. To understand the molecular consequences of stress, detailed genome-wide screens are necessary and need to distinguish between dorsal and ventral hippocampal regions. While transcriptomic screens have become a mainstay in basic and clinical research, proteomic methods are rapidly evolving and hold even greater promise to reveal biologically and clinically relevant biomarkers. METHODS Here, we provide the first combined transcriptomic (RNA sequencing) and proteomic (sequential window acquisition of all theoretical mass spectra [SWATH-MS]) profiling of dorsal and ventral hippocampus in mice. We used three different acute stressors (novelty, swim, and restraint) to assess the impact of stress on both regions. RESULTS We demonstrated that both hippocampal regions display radically distinct molecular responses and that the ventral hippocampus is particularly sensitive to the effects of stress. Separately analyzing these structures greatly increased the sensitivity to detect stress-induced changes. For example, protein interaction cluster analyses revealed a stress-responsive epigenetic network around histone demethylase Kdm6b restricted to the ventral hippocampus, and acute stress reduced methylation of its enzymatic target H3K27me3. Selective Kdm6b knockdown in the ventral hippocampus led to behavioral hyperactivity/hyperresponsiveness. CONCLUSIONS These findings underscore the importance of considering dorsal and ventral hippocampus separately when conducting high-throughput molecular analyses, which has important implications for fundamental research as well as clinical studies.

Statistics

Citations

Dimensions.ai Metrics
2 citations in Web of Science®
5 citations in Scopus®
Google Scholar™

Altmetrics

Downloads

12 downloads since deposited on 29 Jan 2019
12 downloads since 12 months
Detailed statistics

Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > University Children's Hospital Zurich > Medical Clinic
Dewey Decimal Classification:610 Medicine & health
Language:English
Date:1 October 2018
Deposited On:29 Jan 2019 13:54
Last Modified:29 Jan 2019 13:56
Publisher:Elsevier
ISSN:0006-3223
OA Status:Green
Publisher DOI:https://doi.org/10.1016/j.biopsych.2018.02.003
PubMed ID:29605177

Download

Download PDF  'Distinct Proteomic, Transcriptomic, and Epigenetic Stress Responses in Dorsal and Ventral Hippocampus'.
Preview
Content: Published Version
Filetype: PDF
Size: 2MB
View at publisher
Licence: Creative Commons: Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0)