Comorbidity between Alzheimer's disease and major depression: a behavioural and transcriptomic characterization study in mice

Background: Major depression (MD) is the most prevalent psychiatric disease in the population and is considered a prodromal stage of the Alzheimer's disease (AD). Despite both diseases having a robust genetic component, the common transcriptomic signature remains unknown. Methods: We invest...

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Autores: Martín Sánchez, Ana, Piñero González, Janet, 1977-, Nonell Mazelon, Lara, 1972-, Arnal, Magdalena, Ribe, Elena, Nevado-Holgado, Alejo J., Lovestone, Simon, Sanz, Ferran, Furlong, Laura I., 1971-, Valverde Granados, Olga
Formato: artículo
Estado:Versión publicada
Fecha de publicación:2021
País:España
Recursos:Universitat Pompeu Fabra
Repositorio:Repositorio Digital de la UPF
OAI Identifier:oai:repositori.upf.edu:10230/47344
Acesso em linha:http://hdl.handle.net/10230/47344
http://dx.doi.org/10.1186/s13195-021-00810-x
Access Level:acceso abierto
Palavra-chave:Alzheimer’s disease
Behaviour
Comorbidity
Gene Set Enrichment Analysis
Major depression
Transcriptome
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network_acronym_str ES
network_name_str España
repository_id_str
dc.title.none.fl_str_mv Comorbidity between Alzheimer's disease and major depression: a behavioural and transcriptomic characterization study in mice
title Comorbidity between Alzheimer's disease and major depression: a behavioural and transcriptomic characterization study in mice
spellingShingle Comorbidity between Alzheimer's disease and major depression: a behavioural and transcriptomic characterization study in mice
Martín Sánchez, Ana
Alzheimer’s disease
Behaviour
Comorbidity
Gene Set Enrichment Analysis
Major depression
Transcriptome
title_short Comorbidity between Alzheimer's disease and major depression: a behavioural and transcriptomic characterization study in mice
title_full Comorbidity between Alzheimer's disease and major depression: a behavioural and transcriptomic characterization study in mice
title_fullStr Comorbidity between Alzheimer's disease and major depression: a behavioural and transcriptomic characterization study in mice
title_full_unstemmed Comorbidity between Alzheimer's disease and major depression: a behavioural and transcriptomic characterization study in mice
title_sort Comorbidity between Alzheimer's disease and major depression: a behavioural and transcriptomic characterization study in mice
dc.creator.none.fl_str_mv Martín Sánchez, Ana
Piñero González, Janet, 1977-
Nonell Mazelon, Lara, 1972-
Arnal, Magdalena
Ribe, Elena
Nevado-Holgado, Alejo J.
Lovestone, Simon
Sanz, Ferran
Furlong, Laura I., 1971-
Valverde Granados, Olga
author Martín Sánchez, Ana
author_facet Martín Sánchez, Ana
Piñero González, Janet, 1977-
Nonell Mazelon, Lara, 1972-
Arnal, Magdalena
Ribe, Elena
Nevado-Holgado, Alejo J.
Lovestone, Simon
Sanz, Ferran
Furlong, Laura I., 1971-
Valverde Granados, Olga
author_role author
author2 Piñero González, Janet, 1977-
Nonell Mazelon, Lara, 1972-
Arnal, Magdalena
Ribe, Elena
Nevado-Holgado, Alejo J.
Lovestone, Simon
Sanz, Ferran
Furlong, Laura I., 1971-
Valverde Granados, Olga
author2_role author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Alzheimer’s disease
Behaviour
Comorbidity
Gene Set Enrichment Analysis
Major depression
Transcriptome
topic Alzheimer’s disease
Behaviour
Comorbidity
Gene Set Enrichment Analysis
Major depression
Transcriptome
description Background: Major depression (MD) is the most prevalent psychiatric disease in the population and is considered a prodromal stage of the Alzheimer's disease (AD). Despite both diseases having a robust genetic component, the common transcriptomic signature remains unknown. Methods: We investigated the cognitive and emotional behavioural responses in 3- and 6-month-old APP/PSEN1-Tg mice, before β-amyloid plaques were detected. We studied the genetic and pathway deregulation in the prefrontal cortex, striatum, hippocampus and amygdala of mice at both ages, using transcriptomic and functional data analysis. Results: We found that depressive-like and anxiety-like behaviours, as well as memory impairments, are already present at 3-month-old APP/PSEN1-Tg mutant mice together with the deregulation of several genes, such as Ciart, Grin3b, Nr1d1 and Mc4r, and other genes including components of the circadian rhythms, electron transport chain and neurotransmission in all brain areas. Extending these results to human data performing GSEA analysis using DisGeNET database, it provides translational support for common deregulated gene sets related to MD and AD. Conclusions: The present study sheds light on the shared genetic bases between MD and AD, based on a comprehensive characterization from the behavioural to transcriptomic level. These findings suggest that late MD could be an early manifestation of AD.
publishDate 2021
dc.date.none.fl_str_mv 2021
2021
2021
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/10230/47344
http://dx.doi.org/10.1186/s13195-021-00810-x
url http://hdl.handle.net/10230/47344
http://dx.doi.org/10.1186/s13195-021-00810-x
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Alzheimers Res Ther. 2021; 13(1):73
info:eu-repo/grantAgreement/EC/H2020/634143
info:eu-repo/grantAgreement/ES/1PE/SAF2016-75966-R
dc.rights.none.fl_str_mv http://creativecommons.org/licenses/by/4.0/
info:eu-repo/semantics/openAccess
rights_invalid_str_mv http://creativecommons.org/licenses/by/4.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv BioMed Central
publisher.none.fl_str_mv BioMed Central
dc.source.none.fl_str_mv reponame:Repositorio Digital de la UPF
instname:Universitat Pompeu Fabra
instname_str Universitat Pompeu Fabra
reponame_str Repositorio Digital de la UPF
collection Repositorio Digital de la UPF
repository.name.fl_str_mv
repository.mail.fl_str_mv
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spelling Comorbidity between Alzheimer's disease and major depression: a behavioural and transcriptomic characterization study in miceMartín Sánchez, AnaPiñero González, Janet, 1977-Nonell Mazelon, Lara, 1972-Arnal, MagdalenaRibe, ElenaNevado-Holgado, Alejo J.Lovestone, SimonSanz, FerranFurlong, Laura I., 1971-Valverde Granados, OlgaAlzheimer’s diseaseBehaviourComorbidityGene Set Enrichment AnalysisMajor depressionTranscriptomeBackground: Major depression (MD) is the most prevalent psychiatric disease in the population and is considered a prodromal stage of the Alzheimer's disease (AD). Despite both diseases having a robust genetic component, the common transcriptomic signature remains unknown. Methods: We investigated the cognitive and emotional behavioural responses in 3- and 6-month-old APP/PSEN1-Tg mice, before β-amyloid plaques were detected. We studied the genetic and pathway deregulation in the prefrontal cortex, striatum, hippocampus and amygdala of mice at both ages, using transcriptomic and functional data analysis. Results: We found that depressive-like and anxiety-like behaviours, as well as memory impairments, are already present at 3-month-old APP/PSEN1-Tg mutant mice together with the deregulation of several genes, such as Ciart, Grin3b, Nr1d1 and Mc4r, and other genes including components of the circadian rhythms, electron transport chain and neurotransmission in all brain areas. Extending these results to human data performing GSEA analysis using DisGeNET database, it provides translational support for common deregulated gene sets related to MD and AD. Conclusions: The present study sheds light on the shared genetic bases between MD and AD, based on a comprehensive characterization from the behavioural to transcriptomic level. These findings suggest that late MD could be an early manifestation of AD.This study was funded by the EU Medbioinformatic project (grant number 634143), Ministerio de Economia y Competitividad (grant number SAF2016-75966-R-FEDER and PID2019-104077-RB-100) and Ministerio de Sanidad (Retic-ISCIII, RD16/017/010 and Plan Nacional sobre Drogas 2018/007). The Department of Experimental and Health Sciences (UPF) is a “Unidad de Excelencia María de Maeztu” funded by the AEI (CEX2018-000792-M). The Research Programme on Biomedical Informatics (GRIB) is a member of the Spanish National Bioinformatics Institute (INB), funded by ISCIII and FEDER (PT17/0009/0014). The GRIB is also supported by the Agència de Gestió d’Ajuts Universitaris i de Recerca (AGAUR), Generalitat de Catalunya (2017 SGR 00519).BioMed Central202120212021info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdfapplication/pdfhttp://hdl.handle.net/10230/47344http://dx.doi.org/10.1186/s13195-021-00810-xreponame:Repositorio Digital de la UPFinstname:Universitat Pompeu FabraInglésAlzheimers Res Ther. 2021; 13(1):73info:eu-repo/grantAgreement/EC/H2020/634143info:eu-repo/grantAgreement/ES/1PE/SAF2016-75966-R© The Author(s). 2021 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.http://creativecommons.org/licenses/by/4.0/info:eu-repo/semantics/openAccessoai:repositori.upf.edu:10230/473442026-06-12T07:21:37Z
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