Environment-dependent striatal gene expression in the BACHD rat model for Huntington disease.

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State: Public
Version: Final published version
License: CC BY 4.0
Serval ID
serval:BIB_CD7F3608259A
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Environment-dependent striatal gene expression in the BACHD rat model for Huntington disease.
Journal
Scientific reports
Author(s)
Novati A., Hentrich T., Wassouf Z., Weber J.J., Yu-Taeger L., Déglon N., Nguyen H.P., Schulze-Hentrich J.M.
ISSN
2045-2322 (Electronic)
ISSN-L
2045-2322
Publication state
Published
Issued date
11/04/2018
Peer-reviewed
Oui
Volume
8
Number
1
Pages
5803
Language
english
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: epublish
Abstract
Huntington disease (HD) is an autosomal dominant neurodegenerative disorder caused by a mutation in the huntingtin (HTT) gene which results in progressive neurodegeneration in the striatum, cortex, and eventually most brain areas. Despite being a monogenic disorder, environmental factors influence HD characteristics. Both human and mouse studies suggest that mutant HTT (mHTT) leads to gene expression changes that harbor potential to be modulated by the environment. Yet, the underlying mechanisms integrating environmental cues into the gene regulatory program have remained largely unclear. To better understand gene-environment interactions in the context of mHTT, we employed RNA-seq to examine effects of maternal separation (MS) and environmental enrichment (EE) on striatal gene expression during development of BACHD rats. We integrated our results with striatal consensus modules defined on HTT-CAG length and age-dependent co-expression gene networks to relate the environmental factors with disease progression. While mHTT was the main determinant of expression changes, both MS and EE were capable of modulating these disturbances, resulting in distinctive and in several cases opposing effects of MS and EE on consensus modules. This bivalent response to maternal separation and environmental enrichment may aid in explaining their distinct effects observed on disease phenotypes in animal models of HD and related neurodegenerative disorders.
Keywords
Animals, Corpus Striatum/pathology, Disease Models, Animal, Disease Progression, Environmental Exposure, Gene Expression, Gene Expression Profiling, Gene Regulatory Networks, Huntingtin Protein/deficiency, Huntington Disease/pathology, Mice, Rats, Sequence Analysis, RNA
Pubmed
Web of science
Open Access
Yes
Create date
19/04/2018 21:08
Last modification date
09/10/2019 6:09
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