Pharmacoepigenetics of the role of DNA methylation in μ-opioid receptor expression in different human brain regions.
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.



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.



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.
Institute of Clinical Pharmacology, Goethe - University, Theodor-Stern-Kai 7, 60590 Frankfurt am Main, Germany.
Claudia
C
Knothe
Fraunhofer Institute for Molecular Biology & Applied Ecology IME, Project Group Translational Medicine & Pharmacology TMP, Theodor-Stern-Kai 7, 60590 Frankfurt am Main, Germany.
Bruno G
BG
Oertel
DataBionics Research Group, University of Marburg, Hans-Meerwein-Straße, 35032 Marburg, Germany.
Alfred
A
Ultsch
Institute of Legal Medicine, Goethe - University, Kennedyallee 104, 60596 Frankfurt am Main, Germany.
Mattias
M
Kettner
Institute of Legal Medicine, Saarland University, Building 80.2, 66421, Homburg, Saar, Germany.
Peter Harald
PH
Schmidt
Institute of Legal Medicine, Goethe - University, Kennedyallee 104, 60596 Frankfurt am Main, Germany.
Cora
C
Wunder
Institute of Legal Medicine, Goethe - University, Kennedyallee 104, 60596 Frankfurt am Main, Germany.
Stefan W
SW
Toennes
Institute of Clinical Pharmacology, Goethe - University, Theodor-Stern-Kai 7, 60590 Frankfurt am Main, Germany.|Fraunhofer Institute for Molecular Biology & Applied Ecology IME, Project Group Translational Medicine & Pharmacology TMP, Theodor-Stern-Kai 7, 60590 Frankfurt am Main, Germany.
Gerd
G
Geisslinger
Institute of Clinical Pharmacology, Goethe - University, Theodor-Stern-Kai 7, 60590 Frankfurt am Main, Germany.|Fraunhofer Institute for Molecular Biology & Applied Ecology IME, Project Group Translational Medicine & Pharmacology TMP, Theodor-Stern-Kai 7, 60590 Frankfurt am Main, Germany.
Jörn
J
Lötsch
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000701:Analgesics, Opioid / Q000633:toxicity*; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D045744:Cell Line, Tumor; D019175:DNA Methylation; D044127:Epigenesis, Genetic; D005260:Female; D057809:HEK293 Cells; D006801:Humans; D008297:Male; D008875:Middle Aged; D010146:Pain / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D017450:Receptors, Opioid, mu / Q000235:genetics* / Q000378:metabolism; D019966:Substance-Related Disorders / Q000235:genetics* / Q000378:metabolism; D055815:Young Adult
D000701:Analgesics, Opioid; C485764:OPRM1 protein, human; D012333:RNA, Messenger; D017450:Receptors, Opioid, mu
DNA methylation; OPRM1 methylation; human brain; μ-opioid receptor regulation