Title: The IFN<i>γ</i>-PKR Pathway in the Prefrontal Cortex Reactions to Chronic Excessive Alcohol Use
Abstract: Alcoholism: Clinical and Experimental ResearchVolume 39, Issue 3 p. 476-484 Original Article The IFNγ-PKR Pathway in the Prefrontal Cortex Reactions to Chronic Excessive Alcohol Use Shakevia Johnson, Shakevia Johnson Department of Psychiatry and Human Behavior, University of Mississippi Medical Center, Jackson, MississippiSearch for more papers by this authorJeremy Duncan, Jeremy Duncan Department of Psychiatry and Human Behavior, University of Mississippi Medical Center, Jackson, MississippiSearch for more papers by this authorSyed A. Hussain, Syed A. Hussain Department of Psychiatry and Human Behavior, University of Mississippi Medical Center, Jackson, MississippiSearch for more papers by this authorGang Chen, Gang Chen Department of Pharmacology, University of Kentucky College of Medicine, Lexington, KentuckySearch for more papers by this authorJia Luo, Jia Luo Department of Pharmacology, University of Kentucky College of Medicine, Lexington, KentuckySearch for more papers by this authorChanning Mclaurin, Channing Mclaurin Department of Psychiatry and Human Behavior, University of Mississippi Medical Center, Jackson, MississippiSearch for more papers by this authorWarren May, Warren May Department of Medicine, University of Mississippi Medical Center, Jackson, MississippiSearch for more papers by this authorGrazyna Rajkowska, Grazyna Rajkowska Department of Psychiatry and Human Behavior, University of Mississippi Medical Center, Jackson, MississippiSearch for more papers by this authorXiao-Ming Ou, Xiao-Ming Ou Department of Psychiatry and Human Behavior, University of Mississippi Medical Center, Jackson, MississippiSearch for more papers by this authorCraig A. Stockmeier, Craig A. Stockmeier Department of Psychiatry and Human Behavior, University of Mississippi Medical Center, Jackson, Mississippi Department of Psychiatry, Case Western Reserve University, Cleveland, OhioSearch for more papers by this authorJun Ming Wang, Corresponding Author Jun Ming Wang Department of Psychiatry and Human Behavior, University of Mississippi Medical Center, Jackson, Mississippi Department of Pathology, University of Mississippi Medical Center, Jackson, MississippiReprint requests: Jun Ming Wang, PhD, Department of Pathology (N-524), University of Mississippi Medical Center, 2500 N. State Street, Jackson, MS 39216; Tel.: 601-984-4464 (office); Fax: 601-984-5899; E-mail: [email protected] for more papers by this author Shakevia Johnson, Shakevia Johnson Department of Psychiatry and Human Behavior, University of Mississippi Medical Center, Jackson, MississippiSearch for more papers by this authorJeremy Duncan, Jeremy Duncan Department of Psychiatry and Human Behavior, University of Mississippi Medical Center, Jackson, MississippiSearch for more papers by this authorSyed A. Hussain, Syed A. Hussain Department of Psychiatry and Human Behavior, University of Mississippi Medical Center, Jackson, MississippiSearch for more papers by this authorGang Chen, Gang Chen Department of Pharmacology, University of Kentucky College of Medicine, Lexington, KentuckySearch for more papers by this authorJia Luo, Jia Luo Department of Pharmacology, University of Kentucky College of Medicine, Lexington, KentuckySearch for more papers by this authorChanning Mclaurin, Channing Mclaurin Department of Psychiatry and Human Behavior, University of Mississippi Medical Center, Jackson, MississippiSearch for more papers by this authorWarren May, Warren May Department of Medicine, University of Mississippi Medical Center, Jackson, MississippiSearch for more papers by this authorGrazyna Rajkowska, Grazyna Rajkowska Department of Psychiatry and Human Behavior, University of Mississippi Medical Center, Jackson, MississippiSearch for more papers by this authorXiao-Ming Ou, Xiao-Ming Ou Department of Psychiatry and Human Behavior, University of Mississippi Medical Center, Jackson, MississippiSearch for more papers by this authorCraig A. Stockmeier, Craig A. Stockmeier Department of Psychiatry and Human Behavior, University of Mississippi Medical Center, Jackson, Mississippi Department of Psychiatry, Case Western Reserve University, Cleveland, OhioSearch for more papers by this authorJun Ming Wang, Corresponding Author Jun Ming Wang Department of Psychiatry and Human Behavior, University of Mississippi Medical Center, Jackson, Mississippi Department of Pathology, University of Mississippi Medical Center, Jackson, MississippiReprint requests: Jun Ming Wang, PhD, Department of Pathology (N-524), University of Mississippi Medical Center, 2500 N. State Street, Jackson, MS 39216; Tel.: 601-984-4464 (office); Fax: 601-984-5899; E-mail: [email protected] for more papers by this author First published: 19 February 2015 https://doi.org/10.1111/acer.12650Citations: 9Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat 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. Citing Literature Volume39, Issue3March 2015Pages 476-484 RelatedInformation