The IFNγ‐PKR Pathway in the Prefrontal Cortex Reactions to Chronic Excessive Alcohol Use. (19th February 2015)

• Record Type: Journal Article
• Authors: Johnson, Shakevia; Duncan, Jeremy; Hussain, Syed A.; Chen, Gang; Luo, Jia; Mclaurin, Channing; May, Warren; Rajkowska, Grazyna; Ou, Xiao‐Ming; Stockmeier, Craig A.; Wang, Jun Ming
• Is Part Of: Alcoholism. Volume 39:Number 3(2015:Mar.)
• Page Start: 476
• Page End: 484
• Publication Date: 2015-02-19
• Subjects: Alcoholism -- Periodicals; Alcoholism -- Periodicals; Alcoolisme; Electronic journals; Périodique électronique (Descripteur de forme); Ressource Internet (Descripteur de forme); 616.861005
• DOI: 10.1111/acer.12650
• Languages: English
• ISSNs: 0145-6008

Abstract

<abstract abstract-type="main" id="acer12650-abs-0001"> <title> <x xml:space="preserve">Abstract</x> </title> <sec id="acer12650-sec-0001" sec-type="section"> <title>Background</title> <p>Brain cell death is a major pathological consequence of alcohol neurotoxicity. However, the molecular cascades in alcohol‐induced brain tissue injury are unclear.</p> </sec> <sec id="acer12650-sec-0002" sec-type="section"> <title>Methods</title> <p>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<italic>γ</italic>) in the prefrontal cortex (PFC) of postmortem brains from subjects with alcohol use disorders (AUD).</p> </sec> <sec id="acer12650-sec-0003" sec-type="section"> <title>Results</title> <p>The protein levels of PKR, p‐PKR, and IFN<italic>γ</italic> 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.</p> </sec> <sec id="acer12650-sec-0004" sec-type="section"> <title>Conclusions</title> <p>The activation of the IFN<italic>γ</italic>‐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.</p> </sec> </abstract>