title: The IFNγ-PKR pathway in the prefrontal cortex reactions to chronic excessive alcohol use.
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.
authors.affiliation: Department of Psychiatry and Human Behavior, University of Mississippi Medical Center, Jackson, Mississippi.
authors.forename: Shakevia
authors.initials: S
authors.lastname: Johnson
authors.forename: Jeremy
authors.initials: J
authors.lastname: Duncan
authors.forename: Syed A
authors.initials: SA
authors.lastname: Hussain
authors.forename: Gang
authors.initials: G
authors.lastname: Chen
authors.forename: Jia
authors.initials: J
authors.lastname: Luo
authors.forename: Channing
authors.initials: C
authors.lastname: Mclaurin
authors.forename: Warren
authors.initials: W
authors.lastname: May
authors.forename: Grazyna
authors.initials: G
authors.lastname: Rajkowska
authors.forename: Xiao-Ming
authors.initials: XM
authors.lastname: Ou
authors.forename: Craig A
authors.initials: CA
authors.lastname: Stockmeier
authors.forename: Jun Ming
authors.initials: JM
authors.lastname: Wang
mesh_terms: D000328:Adult; D019973:Alcohol-Related Disorders / Q000378:metabolism* / Q000473:pathology; D005260:Female; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis*; D008297:Male; D008875:Middle Aged; D017397:Prefrontal Cortex / Q000378:metabolism* / Q000473:pathology; D015398:Signal Transduction / Q000502:physiology; D019892:eIF-2 Kinase / Q000096:biosynthesis*
chemical_list: D007371:Interferon-gamma; D019892:eIF-2 Kinase
keywords: Alcohol Use Disorders; Human Postmortem Brains; Interferon Gamma; Protein Kinase R