Journal article
The IFN[gamma]-PKR Pathway in the Prefrontal Cortex Reactions to Chronic Excessive Alcohol Use
Alcoholism, clinical and experimental research, Vol.39(3), pp.476-484
03/01/2015
DOI: 10.1111/acer.12650
PMCID: PMC5555843
PMID: 25704249
Abstract
Byline: 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 Keywords: Alcohol Use Disorders; Protein Kinase R; Interferon Gamma; Human Postmortem Brains 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 (IFN[gamma]) in the prefrontal cortex (PFC) of postmortem brains from subjects with alcohol use disorders (AUD). Results The protein levels of PKR, p-PKR, and IFN[gamma] 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 IFN[gamma]-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.
Details
- Title: Subtitle
- The IFN[gamma]-PKR Pathway in the Prefrontal Cortex Reactions to Chronic Excessive Alcohol Use
- Creators
- Shakevia Johnson - University of Mississippi Medical CenterJeremy Duncan - University of Mississippi Medical CenterSyed A Hussain - University of Mississippi Medical CenterGang Chen - University of KentuckyJia Luo - University of KentuckyChanning Mclaurin - University of Mississippi Medical CenterWarren May - University of Mississippi Medical CenterGrazyna Rajkowska - University of Mississippi Medical CenterXiao-Ming OuCraig A Stockmeier - University of Mississippi Medical CenterJun Ming Wang - University of Mississippi Medical Center
- Resource Type
- Journal article
- Publication Details
- Alcoholism, clinical and experimental research, Vol.39(3), pp.476-484
- DOI
- 10.1111/acer.12650
- PMID
- 25704249
- PMCID
- PMC5555843
- NLM abbreviation
- Alcohol Clin Exp Res
- ISSN
- 0145-6008
- eISSN
- 1530-0277
- Publisher
- Wiley Subscription Services, Inc
- Grant note
- name: NIH/NIAAA, award: AA020103, P30 GM103328, MH67996; DOI: 10.13039/100000874, name: The Brain & Behavior Research Foundation (NARSAD); name: University of Mississippi Medical Center
- Language
- English
- Date published
- 03/01/2015
- Description audience
- Academic
- Academic Unit
- Pathology
- Record Identifier
- 9984201246102771
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