Cited by 56Neuroscience and Neuropharmacology ResearchAlcohol Consumption and Health EffectsNeurotransmitter Receptor Influence on Behavior

Astrocyte-specific transcriptome responses to chronic ethanol consumption

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Erickson, Emma K., Farris, Sean P., Blednov, Yuri A., Mayfield, R. Dayne, Harris, R. Adron·2018·The Pharmacogenomics Journal

Abstract

Astrocytes play critical roles in central nervous system (CNS) homeostasis and are implicated in the pathogenesis of neurological and psychiatric conditions, including drug dependence. Little is known about the effects of chronic ethanol consumption on astrocyte gene expression. To address this gap in knowledge, we performed transcriptome-wide RNA sequencing of astrocytes isolated from the prefrontal cortex (PFC) of mice following chronic ethanol consumption. Differential expression analysis revealed ethanol-induced changes unique to astrocytes that were not identified in total homogenate preparations. Astrocyte-specific gene expression revealed calcium-related signaling and regulation of extracellular matrix genes as responses to chronic ethanol use. These findings emphasize the importance of investigating expression changes in specific cellular populations to define molecular consequences of chronic ethanol consumption in mammalian brain.

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  • SLC1A3 was downregulated with alcohol consumption in mouse astrocytes but upregulated in the human alcoholic brain.

    “SLC1A3 (also called “ GLAST ”) was downregulated with alcohol consumption in mouse astrocytes (20,21) but upregulated in the human alcoholic brain (39) .”
  • Recent mouse RNA-seq studies on isolated glial cell types also detected more alcohol-related DEGs in astrocytes than in total brain homogenate and microglia.

    “Recent mouse RNA-seq studies on isolated glial cell types also detected more alcohol-related DEGs in astrocytes than in total brain homogenate (20) and microglia (21) .”
  • The clusters were annotated to seven major brain cell types: excitatory neurons, astrocytes, oligodendrocytes, inhibitory/GABAergic neurons, oligodendrocyte progenitor cells, microglia, and endothelial cells.

    “We then annotated the clusters using the following markers of major brain cell types that are consistently detected in single cell/nucleus transcriptomics studies (7,8,20,23,24) : excitatory neurons, astrocytes, oligodendrocytes, inhibitory/GABAergic neurons, oligodendrocyte progenitor cells (OPCs), microglia, and endothelial cells ( Fig 1C-D ).”

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References 58 · Cited by 56

Authors
Erickson, E. K., Farris, S. P., Blednov, Y. A., Mayfield, R. D., & Harris, R. A.
Affiliations
The University of Texas at Austin (US)
Corresponding author
Erickson, Emma K.
Venue
The Pharmacogenomics Journal
Published
2018-01-05
Volume
18
Issue
4
Pages
578-589
ISSN
  • 1470-269X (ISSN-L)
  • 1473-1150
OpenAlex
W2781920423
Cited by
56
References
58
Citations by year
2026: 8 · 2025: 9 · 2024: 6 · 2023: 7 · 2022: 5 · 2021: 7 · 2020: 8 · 2019: 4 · 2018: 2
FWCI
2.39
Type
journal article
Language
en
Open access
Locations
  • The Pharmacogenomics Journal (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • Instituto Nacional de Investigación y Tecnología Agraria y Alimentaria
  • National Institutes of Health (5r01aa006399-36)
  • National Institute on Alcohol Abuse and Alcoholism (R01-AA006399, F31AA025508, U01AA013520, R01AA012404, U01AA020926)
Topics
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
  • Health Sciences › Medicine › Pathology and Forensic Medicine › Alcohol Consumption and Health Effects
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
Keywords
astrocytes, chronic alcohol consumption, transcriptome, prefrontal cortex, gene expression, calcium signaling, extracellular matrix genes, alcoholism, single-cell RNA sequencing
MeSH terms
Alcohol Drinking, Ethanol, Animals, Astrocytes, Gene Expression Regulation, Humans, Organ Specificity, Prefrontal Cortex, Mice, Transcriptome

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