TY - JOUR
T1 - The IFNγ-PKR pathway in the prefrontal cortex reactions to chronic excessive alcohol use
AU - Johnson, Shakevia
AU - Duncan, Jeremy
AU - Hussain, Syed A.
AU - Chen, Gang
AU - Luo, Jia
AU - Mclaurin, Channing
AU - May, Warren
AU - Rajkowska, Grazyna
AU - Ou, Xiao Ming
AU - Stockmeier, Craig A.
AU - Wang, Jun Ming
N1 - Publisher Copyright:
© 2015 by the Research Society on Alcoholism.
PY - 2015/3/1
Y1 - 2015/3/1
N2 - 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.
AB - 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.
KW - Alcohol Use Disorders
KW - Human Postmortem Brains
KW - Interferon Gamma
KW - Protein Kinase R
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U2 - 10.1111/acer.12650
DO - 10.1111/acer.12650
M3 - Article
C2 - 25704249
AN - SCOPUS:84923848166
SN - 0145-6008
VL - 39
SP - 476
EP - 484
JO - Alcoholism: Clinical and Experimental Research
JF - Alcoholism: Clinical and Experimental Research
IS - 3
ER -