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...
| Autores: | , , , , , , , , , |
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| 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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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. |
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2021 |
| dc.date.none.fl_str_mv |
2021 2021 2021 |
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info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion |
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article |
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publishedVersion |
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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 |
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http://creativecommons.org/licenses/by/4.0/ info:eu-repo/semantics/openAccess |
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http://creativecommons.org/licenses/by/4.0/ |
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openAccess |
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application/pdf application/pdf |
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BioMed Central |
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BioMed Central |
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reponame:Repositorio Digital de la UPF instname:Universitat Pompeu Fabra |
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Universitat Pompeu Fabra |
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Repositorio Digital de la UPF |
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Repositorio Digital de la UPF |
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1869414139075493888 |
| 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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