Stress–response pathways are altered in the hippocampus of chronic alcoholics
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The chronic high-level alcohol consumption seen in alcoholism leads to dramatic effects on the hippocampus, including decreased white matter, loss of oligodendrocytes and other glial cells, and inhibition of neurogenesis. Examining gene expression in post mortem hippocampal tissue from 20 alcoholics and 19 controls allowed us to detect differentially expressed genes that may play a role in the risk for alcoholism or whose expression is modified by chronic consumption of alcohol. We identified 639 named genes whose expression significantly differed between alcoholics and controls at a False Discovery Rate (FDR) ≤ 0.20; 52% of these genes differed by at least 1.2-fold. Differentially expressed genes included the glucocorticoid receptor and the related gene FK506 binding protein 5 (FKBP5), UDP glycosyltransferase 8 (UGT8), urea transporter (SLC14A1), zinc transporter (SLC39A10), Interleukin 1 receptor type 1 (IL1R1), thioredoxin interacting protein (TXNIP), and many metallothioneins. Pathways related to inflammation, hypoxia, and stress showed activation, and pathways that play roles in neurogenesis and myelination showed decreases. The cortisol pathway dysregulation and increased inflammation identified here are seen in other stress-related conditions such as depression and post-traumatic stress disorder and most likely play a role in addiction. Many of the detrimental effects on the hippocampus appear to be mediated through NF-κB signaling. Twenty-four of the differentially regulated genes were previously identified by genome-wide association studies of alcohol use disorders; this raises the potential interest of genes not normally associated with alcoholism, such as suppression of tumorigenicity 18 (ST18), BCL2-associated athanogene 3 (BAG3), and von Willebrand factor (VWF).
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Alcohol exposure triggers changes in gene expression and biological pathways in human brain.
“Alcohol exposure triggers changes in gene expression and biological pathways in human brain.”
From Analysis of whole genome-transcriptomic organization in brain to identify genes associated with alcoholism (2019) · cites this paper as [7]
Transcriptomes from complex tissues such as human brain may be organized into networks of co-expressed genes that better reflect the biological functions and organization of the tissue.
“Transcriptomes from complex tissues, such as human brain, may be organized into networks of co-expressed genes that better reflect the biological functions and organization of the tissue7–14.”
From Analysis of whole genome-transcriptomic organization in brain to identify genes associated with alcoholism (2019) · cites this paper as [7]
mRNA expression studies in human brain showed significant changes in expression of genes related to immune or inflammatory responses in hippocampus and nucleus accumbens.
“Furthermore, mRNA expression studies in human brain showed significant changes in expression of genes related to immune or inflammatory responses in hippocampus7 and nucleus accumbens8.”
From Analysis of whole genome-transcriptomic organization in brain to identify genes associated with alcoholism (2019) · cites this paper as [7]
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Kapoor, M., Wang, J.-C., Farris, S. P., Liu, Y., McClintick, J., Gupta, I., Meyers, J. L., Bertelsen, S., Chao, M., Nurnberger, J., et al. (2019) · Translational Psychiatry · doi:10.1038/s41398-019-0384-y · Cited by 92 · see citing works
Self-citationDaulatzai, M. A. (2015) · Neurotoxicity Research · doi:10.1007/s12640-015-9528-x · Cited by 12 · see citing works
- Authors
- McClintick, J. N., Xuei, X., Tischfield, J. A., Goate, A., Foroud, T., Wetherill, L., Ehringer, M. A., & Edenberg, H. J.
- Affiliations
- Indiana University School of Medicine (US)
- Rutgers, The State University of New Jersey (US)
- Washington University in St. Louis (US)
- University of Colorado Boulder (US)
- Corresponding author
- Edenberg, Howard J.
- ORCID
- Venue
- Alcohol
- Publisher
- Elsevier BV
- Published
- 2013-11
- Volume
- 47
- Issue
- 7
- Pages
- 505-515
- ISSN
- 0741-8329 (ISSN-L)
- PMC
- PMC3836826
- OpenAlex
- W2157152722
- Cited by
- 105
- References
- 96
- Citations by year
- 2026: 6 · 2025: 12 · 2024: 6 · 2023: 9 · 2022: 5 · 2021: 6 · 2020: 9 · 2019: 13 · 2018: 8 · 2017: 5 · 2016: 11 · 2015: 7 · 2014: 8
- FWCI
- 3.93
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Alcohol (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- IUScholarWorks (Indiana University) (submittedVersion)
- Purdue University Indianapolis (Indiana University) (submittedVersion)
- PMC
- Funders
- State University of New York
- Washington University in St. Louis
- University of Connecticut
- Virginia Commonwealth University
- University of Sydney
- National Institutes of Health
- SUNY Downstate Medical Center
- Medical Research Council
- National Health and Medical Research Council
- National Institute on Alcohol Abuse and Alcoholism (Grant U10AA008401, R01AA012725, R01 AA12725, R28AA012725, U10AA008401)
- National Institute on Drug Abuse (Grant U10AA008401)
- Topics
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Health Sciences › Medicine › Epidemiology › Substance Abuse Treatment and Outcomes
- Health Sciences › Medicine › Pathology and Forensic Medicine › Alcohol Consumption and Health Effects
- Keywords
- chronic alcoholism, hippocampus, gene expression, stress response, glucocorticoid receptor, FKBP5, NF-κB signaling, inflammation, hypoxia, neurogenesis, myelination, metallothionein, addiction, alcoholism, postmortem brain
- MeSH terms
- Adult, Aged, Alcoholism, Hypoxia, Female, Hippocampus, Humans, Inflammation, Male, Middle Aged, NF-kappa B, Neurogenesis, Alcoholics, Transcriptome, Gene Ontology
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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