Demethylation of c-MYB binding site mediates upregulation of Bdnf IV in cocaine-conditioned place preference

Scientific Reports
Weiping TianMei Zhao

Abstract

Abnormal BDNF signaling contributes to the structural and behavioral plasticity induced by drugs of abuse. However, the mechanisms regulating expression of Bdnf in drug addiction remain elusive. In the present study, using the conditioned place preference (CPP) model, we showed that expression of Bdnf IV is upregulated in the nucleus accumbens (NAc) of conditioned animals while Bdnf I is upregulated in cocaine-treated mice irrespective of conditioning. The methylation level of a putative c-MYB binding site in the promoter region of Bdnf IV was significantly decreased in the NAc under cocaine CPP conditioning but remained unchanged without conditioning, concurrently with increased binding of c-MYB to this site. Exon IV promoter/luciferase reporter assays revealed that transactivation of Bdnf by c-MYB was blocked by methylation of this c-MYB binding site. Administration of methionine, a precursor of SAM, inhibited cocaine CPP, reversed demethylation of c-MYB binding site and induction of Bdnf IV expression by cocaine CPP. Our results imply that Bdnf IV demethylation at c-MYB binding site is involved in cocaine-triggered seeking behavior, whereas Bdnf I responds to the immediate pharmacological effects of cocaine.

References

Nov 26, 2002·Behavioural Brain Research·Gaetano Di Chiara
Dec 14, 2002·Proceedings of the National Academy of Sciences of the United States of America·L TremolizzoA Guidotti
Jan 30, 2004·Annual Review of Medicine·Jennifer Chao, Eric J Nestler
Oct 7, 2004·Neuropharmacology·Eric J Nestler
Aug 2, 2005·The American Journal of Psychiatry·Peter W Kalivas, Nora D Volkow
Aug 16, 2005·Nature·Glenda C HarrisGary Aston-Jones
Nov 25, 2005·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Ian C G WeaverMoshe Szyf
Jan 21, 2006·Brain Research·Małgorzata FilipMarta Dziedzicka-Wasylewska
Apr 12, 2006·The Journal of Biological Chemistry·Jonathan M LevensonJ David Sweatt
Oct 19, 2006·Journal of Neuroimmunology·Niels KruseFred Lühder
Dec 7, 2006·Journal of Neuroscience Research·Tamara AidTõnis Timmusk
Apr 25, 2007·Nature Reviews. Neuroscience·Nadia TsankovaEric J Nestler
Sep 7, 2007·Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology·Peter W Kalivas, Charles O'Brien
Jan 11, 2008·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Erika D NelsonLisa M Monteggia
Feb 12, 2008·Proceedings of the National Academy of Sciences of the United States of America·Pedro BekinschteinJorge H Medina
Mar 18, 2008·British Journal of Pharmacology·M J ThomasY Shaham
Jul 24, 2008·Neuropharmacology·Scott J RussoEric J Nestler
Sep 19, 2008·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Pascal RomieuJean Zwiller
Oct 17, 2008·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Farah D LubinJ David Sweatt
Oct 30, 2009·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Jerome JeanblancDorit Ron
May 23, 2015·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Ramesh ChandraMary Kay Lobo
May 29, 2015·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Renaud MassartGal Yadid
Jun 13, 2015·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Katherine N WrightMohamed Kabbaj

❮ Previous
Next ❯

Methods Mentioned

BETA
immunoprecipitation
transfection
ChIP
PCR
transfections

Related Concepts

Related Feeds

Basal Ganglia

Basal Ganglia are a group of subcortical nuclei in the brain associated with control of voluntary motor movements, procedural and habit learning, emotion, and cognition. Here is the latest research.