TY - JOUR A1 - Knothe, Claudia A1 - Oertel, Bruno Georg A1 - Ultsch, Alfred A1 - Kettner, Mattias A1 - Schmidt, Peter Harald A1 - Wunder, Cora A1 - Tönnes, Stefan W. A1 - Geisslinger, Gerd A1 - Lötsch, Jörn T1 - Pharmacoepigenetics of the role of DNA methylation in μ-opioid receptor expression in different human brain regions T2 - Epigenomics N2 - Aim: Exposure to opioids has been associated with epigenetic effects. Studies in rodents suggested a role of varying degrees of DNA methylation in the differential regulation of μ-opioid receptor expression across the brain. Methods: In a translational investigation, using tissue acquired postmortem from 21 brain regions of former opiate addicts, representing a human cohort with chronic opioid exposure, μ-opioid receptor expression was analyzed at the level of DNA methylation, mRNA and protein. Results & conclusion: While high or low μ-opioid receptor expression significantly correlated with local OPRM1 mRNA levels, there was no corresponding association with OPRM1 methylation status. Additional experiments in human cell lines showed that changes in DNA methylation associated with changes in μ-opioid expression were an order of magnitude greater than differences in brain. Hence, different degrees of DNA methylation associated with chronic opioid exposure are unlikely to exert a major role in the region-specificity of μ-opioid receptor expression in the human brain. KW - DNA methylation KW - human brain KW - μ-opioid receptor regulation KW - OPRM1 methylation Y1 - 2017 UR - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/43888 UR - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-438887 SN - 1750-192X SN - 1750-1911 N1 - Open access: This work is licensed under the Creative Commons Attribution 4.0 License. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ VL - 8 IS - 12 SP - 1583 EP - 1599 PB - Future Medicine Ltd. CY - London ER -