The IFNγ-PKR pathway in the prefrontal cortex reactions to chronic excessive alcohol use

Shakevia Johnson, Jeremy Duncan, Syed A. Hussain, Gang Chen, Jia Luo, Channing Mclaurin, Warren May, Grazyna Rajkowska, Xiao Ming Ou, Craig A. Stockmeier, Jun Ming Wang

Research output: Contribution to journalArticlepeer-review

10 Scopus citations

Abstract

Background: Brain cell death is a major pathological consequence of alcohol neurotoxicity. However, the molecular cascades in alcohol-induced brain tissue injury are unclear. Methods: Using Western blot and double immunofluorescence, we examined the expression of interferon (IFN)-induced protein kinase R (PKR), phosphorylated-PKR (p-PKR), and IFN gamma (IFNγ) in the prefrontal cortex (PFC) of postmortem brains from subjects with alcohol use disorders (AUD). Results: The protein levels of PKR, p-PKR, and IFNγ were significantly increased in subjects with AUD compared with control subjects without AUD, and a younger age of onset of AUD was significantly correlated with higher protein levels of p-PKR. In addition, elevated PKR- and p-PKR-IR were observed in both neurons and astrocytes in the PFC of subjects with AUD compared to subjects without AUD. Conclusions: The activation of the IFNγ-PKR pathway in PFC of humans is associated with chronic excessive ethanol use with an age of onset dependent manner, and activation of this pathway may play a pivotal role in AUD-related brain tissue injury. This study provides insight into neurodegenerative key factors related to AUD and identifies potential targets for the treatment of alcohol-induced neurotoxicity.

Original languageEnglish
Pages (from-to)476-484
Number of pages9
JournalAlcoholism: Clinical and Experimental Research
Volume39
Issue number3
DOIs
StatePublished - Mar 1 2015

Bibliographical note

Publisher Copyright:
© 2015 by the Research Society on Alcoholism.

Keywords

  • Alcohol Use Disorders
  • Human Postmortem Brains
  • Interferon Gamma
  • Protein Kinase R

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Toxicology
  • Psychiatry and Mental health

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