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A History of Repeated Alcohol Intoxication Promotes Cognitive Impairment and Gene Expression Signatures of Disease Progression in the 3xTg Mouse Model of Alzheimer’s Disease

The impact of alcohol abuse on Alzheimer’s disease (AD) is poorly understood. Here, we show that the onset of neurocognitive impairment in a mouse model of AD is hastened by repeated alcohol intoxication through exposure to alcohol vapor, and we provide a comprehensive gene expression dataset of the...

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Autores principales: Sanna, Pietro Paolo, Cabrelle, Chiara, Kawamura, Tomoya, Mercatelli, Daniele, O'Connor, Nathan, Roberts, Amanda J., Repunte-Canonigo, Vez, Giorgi, Federico M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Society for Neuroscience 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10337838/
https://www.ncbi.nlm.nih.gov/pubmed/37308288
http://dx.doi.org/10.1523/ENEURO.0456-22.2023
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author Sanna, Pietro Paolo
Cabrelle, Chiara
Kawamura, Tomoya
Mercatelli, Daniele
O'Connor, Nathan
Roberts, Amanda J.
Repunte-Canonigo, Vez
Giorgi, Federico M.
author_facet Sanna, Pietro Paolo
Cabrelle, Chiara
Kawamura, Tomoya
Mercatelli, Daniele
O'Connor, Nathan
Roberts, Amanda J.
Repunte-Canonigo, Vez
Giorgi, Federico M.
author_sort Sanna, Pietro Paolo
collection PubMed
description The impact of alcohol abuse on Alzheimer’s disease (AD) is poorly understood. Here, we show that the onset of neurocognitive impairment in a mouse model of AD is hastened by repeated alcohol intoxication through exposure to alcohol vapor, and we provide a comprehensive gene expression dataset of the prefrontal cortex by the single-nucleus RNA sequencing of 113,242 cells. We observed a broad dysregulation of gene expression that involves neuronal excitability, neurodegeneration, and inflammation, including interferon genes. Several genes previously associated with AD in humans by genome-wide association studies were differentially regulated in specific neuronal populations. The gene expression signatures of AD mice with a history of alcohol intoxication showed greater similarity to the signatures of older AD mice with advanced disease and cognitive impairment than did the gene expression signatures of AD mice not exposed to alcohol, suggesting that alcohol promotes transcriptional changes consistent with AD progression. Our gene expression dataset at the single-cell level provides a unique resource for investigations of the molecular bases of the detrimental role of excessive alcohol intake in AD.
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spelling pubmed-103378382023-07-13 A History of Repeated Alcohol Intoxication Promotes Cognitive Impairment and Gene Expression Signatures of Disease Progression in the 3xTg Mouse Model of Alzheimer’s Disease Sanna, Pietro Paolo Cabrelle, Chiara Kawamura, Tomoya Mercatelli, Daniele O'Connor, Nathan Roberts, Amanda J. Repunte-Canonigo, Vez Giorgi, Federico M. eNeuro Research Article: Methods/New Tools The impact of alcohol abuse on Alzheimer’s disease (AD) is poorly understood. Here, we show that the onset of neurocognitive impairment in a mouse model of AD is hastened by repeated alcohol intoxication through exposure to alcohol vapor, and we provide a comprehensive gene expression dataset of the prefrontal cortex by the single-nucleus RNA sequencing of 113,242 cells. We observed a broad dysregulation of gene expression that involves neuronal excitability, neurodegeneration, and inflammation, including interferon genes. Several genes previously associated with AD in humans by genome-wide association studies were differentially regulated in specific neuronal populations. The gene expression signatures of AD mice with a history of alcohol intoxication showed greater similarity to the signatures of older AD mice with advanced disease and cognitive impairment than did the gene expression signatures of AD mice not exposed to alcohol, suggesting that alcohol promotes transcriptional changes consistent with AD progression. Our gene expression dataset at the single-cell level provides a unique resource for investigations of the molecular bases of the detrimental role of excessive alcohol intake in AD. Society for Neuroscience 2023-07-04 /pmc/articles/PMC10337838/ /pubmed/37308288 http://dx.doi.org/10.1523/ENEURO.0456-22.2023 Text en Copyright © 2023 Sanna et al. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution and reproduction in any medium provided that the original work is properly attributed.
spellingShingle Research Article: Methods/New Tools
Sanna, Pietro Paolo
Cabrelle, Chiara
Kawamura, Tomoya
Mercatelli, Daniele
O'Connor, Nathan
Roberts, Amanda J.
Repunte-Canonigo, Vez
Giorgi, Federico M.
A History of Repeated Alcohol Intoxication Promotes Cognitive Impairment and Gene Expression Signatures of Disease Progression in the 3xTg Mouse Model of Alzheimer’s Disease
title A History of Repeated Alcohol Intoxication Promotes Cognitive Impairment and Gene Expression Signatures of Disease Progression in the 3xTg Mouse Model of Alzheimer’s Disease
title_full A History of Repeated Alcohol Intoxication Promotes Cognitive Impairment and Gene Expression Signatures of Disease Progression in the 3xTg Mouse Model of Alzheimer’s Disease
title_fullStr A History of Repeated Alcohol Intoxication Promotes Cognitive Impairment and Gene Expression Signatures of Disease Progression in the 3xTg Mouse Model of Alzheimer’s Disease
title_full_unstemmed A History of Repeated Alcohol Intoxication Promotes Cognitive Impairment and Gene Expression Signatures of Disease Progression in the 3xTg Mouse Model of Alzheimer’s Disease
title_short A History of Repeated Alcohol Intoxication Promotes Cognitive Impairment and Gene Expression Signatures of Disease Progression in the 3xTg Mouse Model of Alzheimer’s Disease
title_sort history of repeated alcohol intoxication promotes cognitive impairment and gene expression signatures of disease progression in the 3xtg mouse model of alzheimer’s disease
topic Research Article: Methods/New Tools
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10337838/
https://www.ncbi.nlm.nih.gov/pubmed/37308288
http://dx.doi.org/10.1523/ENEURO.0456-22.2023
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