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.
eNeuro
; 10(7)2023 Jul.
Article
en En
| MEDLINE
| ID: mdl-37308288
ABSTRACT
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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Texto completo:
1
Base de datos:
MEDLINE
Asunto principal:
Intoxicación Alcohólica
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Enfermedad de Alzheimer
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Disfunción Cognitiva
Tipo de estudio:
Prognostic_studies
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Risk_factors_studies
Idioma:
En
Revista:
ENeuro
Año:
2023
Tipo del documento:
Article