title: Demethylation of c-MYB binding site mediates upregulation of Bdnf IV in cocaine-conditioned place preference.
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.
authors.affiliation: Key Lab of Mental Health, Institute of Psychology, Chinese Academy of Sciences, 16 Lincui Rd., Beijing 100101, China.|Tianjin Research Center of Basic Medical Science, Tianjin Medical University, Tianjin, 300070, China.
authors.forename: Weiping
authors.initials: W
authors.lastname: Tian
authors.affiliation: Key Lab of Mental Health, Institute of Psychology, Chinese Academy of Sciences, 16 Lincui Rd., Beijing 100101, China.|Beijing Institutes of Life Science, Chinese Academy of Sciences, Beijing 100101, China.
authors.forename: Jiesi
authors.initials: J
authors.lastname: Wang
authors.affiliation: Key Lab of Mental Health, Institute of Psychology, Chinese Academy of Sciences, 16 Lincui Rd., Beijing 100101, China.
authors.forename: Ke
authors.initials: K
authors.lastname: Zhang
authors.affiliation: Beijing Institutes of Life Science, Chinese Academy of Sciences, Beijing 100101, China.
authors.forename: Huajing
authors.initials: H
authors.lastname: Teng
authors.affiliation: Key Lab of Mental Health, Institute of Psychology, Chinese Academy of Sciences, 16 Lincui Rd., Beijing 100101, China.
authors.forename: Chong
authors.initials: C
authors.lastname: Li
authors.affiliation: McGill University, Department of Pharmacology and Therapeutics, Montréal, Québec, Canada H3G 1Y6.
authors.forename: Moshe
authors.initials: M
authors.lastname: Szyf
authors.affiliation: Beijing Institutes of Life Science, Chinese Academy of Sciences, Beijing 100101, China.|Institute of Genomic Medicine, Wenzhou Medical College, University-town, Wenzhou, Zhejiang, 325000, China.
authors.forename: Zhong Sheng
authors.initials: ZS
authors.lastname: Sun
authors.affiliation: Key Lab of Mental Health, Institute of Psychology, Chinese Academy of Sciences, 16 Lincui Rd., Beijing 100101, China.
authors.forename: Mei
authors.initials: M
authors.lastname: Zhao
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D019208:Brain-Derived Neurotrophic Factor / Q000096:biosynthesis*; D003042:Cocaine / Q000009:adverse effects* / Q000494:pharmacology; D019970:Cocaine-Related Disorders / Q000378:metabolism*; D019175:DNA Methylation / Q000187:drug effects*; D008297:Male; D051379:Mice; D020598:Proto-Oncogene Proteins c-myb; D020218:Response Elements; D015854:Up-Regulation / Q000187:drug effects*
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D020598:Proto-Oncogene Proteins c-myb; D003042:Cocaine