Luana Martins De Carvalho1,2, Corinde E Wiers1,3, Hui Sun1, Gene-Jack Wang1, Nora D Volkow1,4. 1. National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, MD, USA. 2. Center for Alcohol Research in Epigenetics, Department of Psychiatry, University of Illinois at Chicago, Chicago, IL, USA. 3. Department of Psychiatry, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA. 4. National Institute on Drug Abuse, National Institutes of Health, Rockville, MD, USA.
Abstract
INTRODUCTION: Repeated exposure to high doses of alcohol triggers neuroinflammatory processes that contribute to craving and mood dysfunction in alcohol use disorder (AUD). The upregulation of the translocator protein (TSPO) is considered a biomarker of neuroinflammation, and TSPO ligands have been used as neuroimaging biomarkers of neuroinflammation. Epigenetic mechanisms are also implicated in neuroinflammatory responses to alcohol, and elevated expression of HDAC2 and HDAC6 has been reported in the brain of animals exposed to chronic alcohol. METHODS: The present study examined the transcriptional regulation of TSPO, HDAC2, and HDAC6 in human postmortem brain tissue from males previously diagnosed with AUD (n = 11) compared to age-matched nondependent males (n = 13) in four brain regions relevant to AUD: prefrontal cortex (PFC), nucleus accumbens (NAc), hippocampus (HPP), and amygdala (AMY). RESULTS: Translocator protein mRNA levels in AMY and PFC and HDAC2 and HDAC6 mRNA levels in AMY were upregulated in AUD compared to controls. In AMY, TSPO mRNA levels were positively associated with HDAC2 and HDAC6 mRNA levels, suggesting a possible regulation of TSPO by HDAC2 and HDAC6 in this brain region. In contrast, there were no group differences for TSPO, HDAC2, and HDAC6 in NAc and HPP. CONCLUSION: Our study is the first to find upregulated TSPO mRNA levels in AMY and PFC in postmortem brains from AUD consistent with neuroinflammation, and in the amygdala, they implicate epigenetic regulation of TSPO by HDAC2 and HDAC6.
INTRODUCTION: Repeated exposure to high doses of alcohol triggers neuroinflammatory processes that contribute to craving and mood dysfunction in alcohol use disorder (AUD). The upregulation of the translocator protein (TSPO) is considered a biomarker of neuroinflammation, and TSPO ligands have been used as neuroimaging biomarkers of neuroinflammation. Epigenetic mechanisms are also implicated in neuroinflammatory responses to alcohol, and elevated expression of HDAC2 and HDAC6 has been reported in the brain of animals exposed to chronic alcohol. METHODS: The present study examined the transcriptional regulation of TSPO, HDAC2, and HDAC6 in human postmortem brain tissue from males previously diagnosed with AUD (n = 11) compared to age-matched nondependent males (n = 13) in four brain regions relevant to AUD: prefrontal cortex (PFC), nucleus accumbens (NAc), hippocampus (HPP), and amygdala (AMY). RESULTS: Translocator protein mRNA levels in AMY and PFC and HDAC2 and HDAC6 mRNA levels in AMY were upregulated in AUD compared to controls. In AMY, TSPO mRNA levels were positively associated with HDAC2 and HDAC6 mRNA levels, suggesting a possible regulation of TSPO by HDAC2 and HDAC6 in this brain region. In contrast, there were no group differences for TSPO, HDAC2, and HDAC6 in NAc and HPP. CONCLUSION: Our study is the first to find upregulated TSPO mRNA levels in AMY and PFC in postmortem brains from AUD consistent with neuroinflammation, and in the amygdala, they implicate epigenetic regulation of TSPO by HDAC2 and HDAC6.
Authors: John Peyton Bohnsack; Benjamin A Hughes; Todd K O'Buckley; Kamyra Edokpolor; Joyce Besheer; A Leslie Morrow Journal: Neuropsychopharmacology Date: 2018-02-27 Impact factor: 7.853
Authors: Juan Liu; Andrew R Yang; Timothy Kelly; Adam Puche; Chioma Esoga; Harry L June; Ahmed Elnabawi; Istvan Merchenthaler; Werner Sieghart; Harry L June; Laure Aurelian Journal: Proc Natl Acad Sci U S A Date: 2011-02-28 Impact factor: 11.205
Authors: Corinde E Wiers; Leandro F Vendruscolo; Jan-Willem van der Veen; Peter Manza; Ehsan Shokri-Kojori; Danielle S Kroll; Dana E Feldman; Katherine L McPherson; Catherine L Biesecker; Rui Zhang; Kimberly Herman; Sophie K Elvig; Janaina C M Vendruscolo; Sara A Turner; Shanna Yang; Melanie Schwandt; Dardo Tomasi; Mackenzie C Cervenka; Anders Fink-Jensen; Helene Benveniste; Nancy Diazgranados; Gene-Jack Wang; George F Koob; Nora D Volkow Journal: Sci Adv Date: 2021-04-09 Impact factor: 14.136
Authors: Lindsay R Meredith; Elizabeth M Burnette; Erica N Grodin; Michael R Irwin; Lara A Ray Journal: Brain Behav Immun Date: 2021-07-31 Impact factor: 19.227