Stress-response pathways are altered in the hippocampus of chronic alcoholics

Jeanette McClintick, Xiaoling Xuei, Jay A. Tischfield, Alison Goate, Tatiana Foroud, Leah Wetherill, Marissa A. Ehringer, Howard Edenberg

Research output: Contribution to journalArticle

39 Citations (Scopus)

Abstract

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).

Original languageEnglish
Pages (from-to)505-515
Number of pages11
JournalAlcohol
Volume47
Issue number7
DOIs
StatePublished - Nov 2013

Fingerprint

Alcoholics
alcoholism
Hippocampus
Genes
Alcoholism
Neurogenesis
Alcohol Drinking
Alcohols
alcohol
Gene expression
Interleukin-1 Type I Receptors
Inflammation
Gene Expression
posttraumatic stress disorder
role play
Glycosyltransferases
Thioredoxins
suppression
alcohol consumption
Uridine Diphosphate

Keywords

  • Alcoholism
  • Cortisol
  • Gene expression
  • GWAS
  • Hippocampus
  • Inflammation
  • NF-κB
  • Stress

ASJC Scopus subject areas

  • Biochemistry
  • Medicine(all)
  • Behavioral Neuroscience
  • Neurology
  • Toxicology
  • Health(social science)

Cite this

Stress-response pathways are altered in the hippocampus of chronic alcoholics. / McClintick, Jeanette; Xuei, Xiaoling; Tischfield, Jay A.; Goate, Alison; Foroud, Tatiana; Wetherill, Leah; Ehringer, Marissa A.; Edenberg, Howard.

In: Alcohol, Vol. 47, No. 7, 11.2013, p. 505-515.

Research output: Contribution to journalArticle

McClintick, J, Xuei, X, Tischfield, JA, Goate, A, Foroud, T, Wetherill, L, Ehringer, MA & Edenberg, H 2013, 'Stress-response pathways are altered in the hippocampus of chronic alcoholics', Alcohol, vol. 47, no. 7, pp. 505-515. https://doi.org/10.1016/j.alcohol.2013.07.002
McClintick, Jeanette ; Xuei, Xiaoling ; Tischfield, Jay A. ; Goate, Alison ; Foroud, Tatiana ; Wetherill, Leah ; Ehringer, Marissa A. ; Edenberg, Howard. / Stress-response pathways are altered in the hippocampus of chronic alcoholics. In: Alcohol. 2013 ; Vol. 47, No. 7. pp. 505-515.
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