Pharmacoepigenetics of the role of DNA methylation in μ-opioid receptor expression in different human brain regions
- 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.
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| Author: | Claudia Knothe, Bruno Georg OertelGND, Alfred UltschGND, Mattias KettnerORCiDGND, Peter Harald Schmidt, Cora WunderORCiDGND, Stefan W. TönnesORCiD, Gerd GeisslingerORCiDGND, Jörn LötschORCiDGND |
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| URN: | urn:nbn:de:hebis:30:3-438887 |
| DOI: | https://doi.org/10.2217/epi-2016-0072 |
| ISSN: | 1750-192X |
| ISSN: | 1750-1911 |
| Pubmed Id: | https://pubmed.ncbi.nlm.nih.gov/27685027 |
| Parent Title (English): | Epigenomics |
| Publisher: | Future Medicine Ltd. |
| Place of publication: | London |
| Contributor(s): | Michael J. Parnham |
| Document Type: | Article |
| Language: | English |
| Date of Publication (online): | 2017/10/24 |
| Year of first Publication: | 2016 |
| Publishing Institution: | Universitätsbibliothek Johann Christian Senckenberg |
| Release Date: | 2017/10/24 |
| Tag: | DNA methylation; OPRM1 methylation; human brain; μ-opioid receptor regulation |
| Volume: | 8 |
| Issue: | 12 |
| Page Number: | 17 |
| First Page: | 1583 |
| Last Page: | 1599 |
| Note: | 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/ |
| HeBIS-PPN: | 428607357 |
| Institutes: | Medizin / Medizin |
| Dewey Decimal Classification: | 6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit |
| Sammlungen: | Universitätspublikationen |
| Licence (German): |  Creative Commons - Namensnennung 4.0 |
