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Demethylation of c-MYB binding site mediates upregulation of Bdnf IV in cocaine-conditioned place preference
Tian, Weiping1,2; Wang JS(王杰思)1,3; Zhang, Ke1; Teng, Huajing3; Li, Chong1; Szyf, Moshe5; Sun, Zhong Sheng3,4; Zhao, Mei1
2016-02-25
Source PublicationSCIENTIFIC REPORTS
ISSN2045-2322
SubtypeArticle
Volume6Issue:22Pages:087
AbstractAbnormal 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.
DOI10.1038/srep22087
Indexed BySCI
Language英语
Funding OrganizationNatural Science Foundation of China(30870821 ; Key Project of the National 12th Five-Year Research Program of China(2012BAI03B02) ; National Natural Science Foundation of China(91132728) ; Tianjin Municipal Education Commission(20130601) ; 81071078)
WOS Research AreaScience & Technology - Other Topics
WOS SubjectMultidisciplinary Sciences
WOS IDWOS:000370800800002
WOS HeadingsScience & Technology
WOS KeywordMESOLIMBIC DOPAMINE SYSTEM ; NEUROTROPHIC FACTOR ; DNA METHYLATION ; TRANSCRIPTION FACTOR ; DRUG-ADDICTION ; EPIGENETIC REGULATION ; NUCLEUS-ACCUMBENS ; SPLICE VARIANTS ; BRAIN ; EXPRESSION
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Cited Times:3[WOS]   [WOS Record]     [Related Records in WOS]
Document Type期刊论文
Identifierhttp://ir.psych.ac.cn/handle/311026/19586
Collection中国科学院心理健康重点实验室
Affiliation1.Chinese Acad Sci, Inst Psychol, Key Lab Mental Hlth, 16 Lincui Rd, Beijing 100101, Peoples R China
2.Tianjin Med Univ, Tianjin Res Ctr Basic Med Sci, Tianjin 300070, Peoples R China
3.Chinese Acad Sci, Beijing Inst Life Sci, Beijing 100101, Peoples R China
4.Univ Town, Wenzhou Med Coll, Inst Genom Med, Wenzhou 325000, Zhejiang, Peoples R China
5.McGill Univ, Dept Pharmacol & Therapeut, Montreal, PQ H3G 1Y6, Canada
First Author AffilicationKey Laboratory of Mental Health, CAS
Recommended Citation
GB/T 7714
Tian, Weiping,Wang JS,Zhang, Ke,et al. Demethylation of c-MYB binding site mediates upregulation of Bdnf IV in cocaine-conditioned place preference[J]. SCIENTIFIC REPORTS,2016,6(22):087.
APA Tian, Weiping.,Wang JS.,Zhang, Ke.,Teng, Huajing.,Li, Chong.,...&Zhao, Mei.(2016).Demethylation of c-MYB binding site mediates upregulation of Bdnf IV in cocaine-conditioned place preference.SCIENTIFIC REPORTS,6(22),087.
MLA Tian, Weiping,et al."Demethylation of c-MYB binding site mediates upregulation of Bdnf IV in cocaine-conditioned place preference".SCIENTIFIC REPORTS 6.22(2016):087.
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