ArticleNature neuroscience2015
Epigenetic basis of opiate suppression of Bdnf gene expression in the ventral tegmental area.
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Article in Nature neuroscience, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 58 papers.
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58citing papers in PubMed
6.2field-weighted citation impact, top 2% of its field
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58 citing papers in PubMed, 106 citations in OpenAlex.
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Authors and funding
32 authors at 6 institutions in 2 countries.
Ja Wook KooFishberg Department of Neuroscience and Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
Michelle S Mazei-Robison1] Fishberg Department of Neuroscience and Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, New York, USA. [2] Department of Physiology, Michigan State University, East Lansing, Michigan, USA.
Quincey LaPlantFishberg Department of Neuroscience and Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
Gabor Egervari1] Fishberg Department of Neuroscience and Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, New York, USA. [2] Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, New York, USA. [3] Department of Pharmacology and Systems Therapeutics, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
Kevin M BraunscheidelDepartment of Pharmacology and Toxicology, The State University of New York at Buffalo, Buffalo, New York, USA.
Danielle N AdankDepartment of Pharmacology and Toxicology, The State University of New York at Buffalo, Buffalo, New York, USA.
Deveroux FergusonFishberg Department of Neuroscience and Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
Jian FengFishberg Department of Neuroscience and Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
Haosheng SunFishberg Department of Neuroscience and Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
Kimberly N ScobieFishberg Department of Neuroscience and Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
Diane M Damez-WernoFishberg Department of Neuroscience and Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
Efrain RibeiroFishberg Department of Neuroscience and Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
Catherine Jensen PeñaFishberg Department of Neuroscience and Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, New York, USA.ORCID 0000000228845035
Deena WalkerFishberg Department of Neuroscience and Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
Rosemary C BagotFishberg Department of Neuroscience and Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
Michael E CahillFishberg Department of Neuroscience and Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
Sarah Ann R Anderson1] Fishberg Department of Neuroscience and Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, New York, USA. [2] Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, New York, USA. [3] Department of Pharmacology and Systems Therapeutics, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
Benoit LabontéFishberg Department of Neuroscience and Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
Georgia E HodesFishberg Department of Neuroscience and Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
Heidi BrowneFishberg Department of Neuroscience and Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
Benjamin Chadwick1] Fishberg Department of Neuroscience and Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, New York, USA. [2] Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, New York, USA. [3] Department of Pharmacology and Systems Therapeutics, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
Alfred J Robison1] Fishberg Department of Neuroscience and Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, New York, USA. [2] Department of Physiology, Michigan State University, East Lansing, Michigan, USA.
Vincent F Vialou1] Fishberg Department of Neuroscience and Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, New York, USA. [2] Institut National de la Santé et de la Recherche Médicale, U952, Centre National de la Recherche Scientifique, Unité Mixte de Recherche 7224, UPMC, Paris, France.
Caroline DiasFishberg Department of Neuroscience and Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
Zachary LorschFishberg Department of Neuroscience and Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
Ezekiell MouzonFishberg Department of Neuroscience and Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
Mary Kay LoboDepartment of Anatomy and Neurobiology, University of Maryland School of Medicine, Baltimore, Maryland, USA.
David M DietzInstitut National de la Santé et de la Recherche Médicale, U952, Centre National de la Recherche Scientifique, Unité Mixte de Recherche 7224, UPMC, Paris, France.
Scott J RussoFishberg Department of Neuroscience and Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
Rachael L NeveDepartment of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA.
Yasmin L Hurd1] Fishberg Department of Neuroscience and Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, New York, USA. [2] Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, New York, USA. [3] Department of Pharmacology and Systems Therapeutics, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
Eric J NestlerFishberg Department of Neuroscience and Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
Allen Institute for Brain Science · USUniversity at Buffalo, State University of New York · USIcahn School of Medicine at Mount Sinai · USInserm · FRInstitute of Cognitive and Brain Sciences · USUniversity of Maryland, Baltimore · US
Funding
TRANSGENIC COREP01DA008227 · NIDA · YALE UNIVERSITY · PI NESTLER, ERIC J. · 1993 to 2018
$28.1MNeurotrophic Mechanisms in Opiate and Cocaine ActionR01DA014133 · NIDA · UT SOUTHWESTERN MEDICAL CENTER · PI ERIC J. NESTLER · 2000 to 2026
$12.1MThe Opioid mesolimbic system in heroin abuseR01DA015446 · NIDA · KAROLINSKA INSTITUTE · PI HURD, YASMIN L. · 2002 to 2018
$7.1MCocaine-induced mitochondrial mechanisms and molecular mediators in reward circuitryR01DA038613 · NIDA · UNIVERSITY OF MARYLAND BALTIMORE · PI LOBO, MARY KAY · 2014 to 2025
$4.9MTRAINING IN PHARMACOLOGY OF DRUGS OF ABUSET32DA007135 · NIDA · MOUNT SINAI SCHOOL OF MEDICINE OF NYU · PI DEVI, LAKSHMI A · 1985 to 2018
$4.9MNIDA NIH HHS P01 DA008227NIDA NIH HHS R01 DA014133NIDA NIH HHS R01 DA015446NIDA NIH HHS R01 DA038613NIDA NIH HHS T32 DA007135
Abstract
Brain-derived neurotrophic factor (BDNF) has a crucial role in modulating neural and behavioral plasticity to drugs of abuse. We found a persistent downregulation of exon-specific Bdnf expression in the ventral tegmental area (VTA) in response to chronic opiate exposure, which was mediated by specific epigenetic modifications at the corresponding Bdnf gene promoters. Exposure to chronic morphine increased stalling of RNA polymerase II at these Bdnf promoters in VTA and altered permissive and repressive histone modifications and occupancy of their regulatory proteins at the specific promoters. Furthermore, we found that morphine suppressed binding of phospho-CREB (cAMP response element binding protein) to Bdnf promoters in VTA, which resulted from enrichment of trimethylated H3K27 at the promoters, and that decreased NURR1 (nuclear receptor related-1) expression also contributed to Bdnf repression and associated behavioral plasticity to morphine. Our findings suggest previously unknown epigenetic mechanisms of morphine-induced molecular and behavioral neuroadaptations.
Indexed as
Analgesics, OpioidAnimalsBrain-Derived Neurotrophic FactorCocaineConditioning, OperantDopamine Uptake InhibitorsEnhancer of Zeste Homolog 2 ProteinEpigenesis, GeneticHeroin DependenceHumansMaleMiceMice, Inbred C57BLMice, TransgenicMotor ActivityPolycomb Repressive Complex 2Analgesics, OpioidBrain-Derived Neurotrophic FactorCocaineDopamine Uptake InhibitorsEnhancer of Zeste Homolog 2 ProteinEzh2 protein, mousePolycomb Repressive Complex 2RNA Polymerase II
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