Comorbidity between Alzheimer’s disease and major depression: a behavioural and transcriptomic characterization study in mice
Abstract 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 investig...
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| Format: | Article |
| Language: | English |
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BMC
2021-04-01
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| Series: | Alzheimer’s Research & Therapy |
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| Online Access: | https://doi.org/10.1186/s13195-021-00810-x |
| _version_ | 1829532750632189952 |
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| author | Ana Martín-Sánchez Janet Piñero Lara Nonell Magdalena Arnal Elena M. Ribe Alejo Nevado-Holgado Simon Lovestone Ferran Sanz Laura I. Furlong Olga Valverde |
| author_facet | Ana Martín-Sánchez Janet Piñero Lara Nonell Magdalena Arnal Elena M. Ribe Alejo Nevado-Holgado Simon Lovestone Ferran Sanz Laura I. Furlong Olga Valverde |
| author_sort | Ana Martín-Sánchez |
| collection | DOAJ |
| description | Abstract 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. |
| first_indexed | 2024-12-16T18:44:21Z |
| format | Article |
| id | doaj.art-4bb29b8200dd48c7a1e162b9f080fde8 |
| institution | Directory Open Access Journal |
| issn | 1758-9193 |
| language | English |
| last_indexed | 2024-12-16T18:44:21Z |
| publishDate | 2021-04-01 |
| publisher | BMC |
| record_format | Article |
| series | Alzheimer’s Research & Therapy |
| spelling | doaj.art-4bb29b8200dd48c7a1e162b9f080fde82022-12-21T22:20:53ZengBMCAlzheimer’s Research & Therapy1758-91932021-04-0113111910.1186/s13195-021-00810-xComorbidity between Alzheimer’s disease and major depression: a behavioural and transcriptomic characterization study in miceAna Martín-Sánchez0Janet Piñero1Lara Nonell2Magdalena Arnal3Elena M. Ribe4Alejo Nevado-Holgado5Simon Lovestone6Ferran Sanz7Laura I. Furlong8Olga Valverde9Neurobiology of Behaviour Research Group (GReNeC-NeuroBio), Department of Experimental and Health Science, Universitat Pompeu FabraResearch Programme on Biomedical Informatics (GRIB), IMIM-Hospital del Mar Medical Research Institute, Universitat Pompeu FabraResearch Programme on Biomedical Informatics (GRIB), IMIM-Hospital del Mar Medical Research Institute, Universitat Pompeu FabraResearch Programme on Biomedical Informatics (GRIB), IMIM-Hospital del Mar Medical Research Institute, Universitat Pompeu FabraDepartment of Psychiatry, University of OxfordDepartment of Psychiatry, University of OxfordDepartment of Psychiatry, University of OxfordResearch Programme on Biomedical Informatics (GRIB), IMIM-Hospital del Mar Medical Research Institute, Universitat Pompeu FabraResearch Programme on Biomedical Informatics (GRIB), IMIM-Hospital del Mar Medical Research Institute, Universitat Pompeu FabraNeurobiology of Behaviour Research Group (GReNeC-NeuroBio), Department of Experimental and Health Science, Universitat Pompeu FabraAbstract 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.https://doi.org/10.1186/s13195-021-00810-xAlzheimer’s diseaseMajor depressionGene Set Enrichment AnalysisComorbidityTranscriptomeBehaviour |
| spellingShingle | Ana Martín-Sánchez Janet Piñero Lara Nonell Magdalena Arnal Elena M. Ribe Alejo Nevado-Holgado Simon Lovestone Ferran Sanz Laura I. Furlong Olga Valverde Comorbidity between Alzheimer’s disease and major depression: a behavioural and transcriptomic characterization study in mice Alzheimer’s Research & Therapy Alzheimer’s disease Major depression Gene Set Enrichment Analysis Comorbidity Transcriptome Behaviour |
| title | 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_short | 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 |
| topic | Alzheimer’s disease Major depression Gene Set Enrichment Analysis Comorbidity Transcriptome Behaviour |
| url | https://doi.org/10.1186/s13195-021-00810-x |
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