Dnmt3a regulates emotional behavior and spine plasticity in the nucleus accumbens

被引：448

作者：

LaPlant, Quincey ^{[1
,2
]}

Vialou, Vincent ^{[1
]}

Covington, Herbert E., III ^{[1
]}

Dumitriu, Dani ^{[1
]}

Feng, Jian ^{[1
]}

Warren, Brandon L. ^{[1
,3
]}

Maze, Ian ^{[1
]}

Dietz, David M. ^{[1
]}

Watts, Emily L. ^{[1
]}

Iniguez, Sergio D. ^{[1
,3
]}

Koo, Ja Wook ^{[1
]}

Mouzon, Ezekiell ^{[1
]}

Renthal, William ^{[2
]}

Hollis, Fiona ^{[4
]}

Wang, Hui ^{[4
]}

Noonan, Michele A. ^{[2
]}

Ren, Yanhua ^{[1
]}

Eisch, Amelia J. ^{[2
]}

Bolanos, Carlos A. ^{[3
]}

Kabbaj, Mohamed ^{[4
]}

Xiao, Guanghua ^{[5
]}

Neve, Rachael L. ^{[6
]}

Hurd, Yasmin L. ^{[1
]}

Oosting, Ronald S. ^{[1
,7
]}

Fan, Gouping ^{[8
]}

Morrison, John H. ^{[1
]}

Nestler, Eric J. ^{[1
]}

机构：

[1] Mt Sinai Sch Med, Fishberg Dept Neurosci, New York, NY USA

[2] Univ Texas SW Med Ctr Dallas, Dept Psychiat, Dallas, TX 75390 USA

[3] Florida State Univ, Dept Psychol, Tallahassee, FL 32306 USA

[4] Florida State Univ, Dept Biomed Sci, Tallahassee, FL 32306 USA

[5] Univ Texas SW Med Ctr Dallas, Dept Clin Sci, Dallas, TX 75390 USA

[6] MIT, Dept Brain & Cognit Sci, Cambridge, MA 02139 USA

[7] Univ Utrecht, Dept Pharmacol, Utrecht Inst Pharmaceut Sci, Utrecht, Netherlands

[8] Univ Calif Los Angeles, David Geffen Sch Med, Dept Human Genet, Los Angeles, CA 90095 USA

来源：

NATURE NEUROSCIENCE | 2010年 / 13卷 / 09期

关键词：

COCAINE-INDUCED PLASTICITY; DENDRITIC SPINES; DNA METHYLATION; CHROMATIN REGULATION; SYNAPTIC PLASTICITY; PREFRONTAL CORTEX; IN-VIVO; NEURONS; INCREASES; REWARD;

D O I：

10.1038/nn.2619

中图分类号：

Q189 [神经科学];

学科分类号：

071006 ;

摘要：

Despite abundant expression of DNA methyltransferases (Dnmts) in brain, the regulation and behavioral role of DNA methylation remain poorly understood. We found that Dnmt3a expression was regulated in mouse nucleus accumbens (NAc) by chronic cocaine use and chronic social defeat stress. Moreover, NAc-specific manipulations that block DNA methylation potentiated cocaine reward and exerted antidepressant-like effects, whereas NAc-specific Dnmt3a overexpression attenuated cocaine reward and was pro-depressant. On a cellular level, we found that chronic cocaine use selectively increased thin dendritic spines on NAc neurons and that DNA methylation was both necessary and sufficient to mediate these effects. These data establish the importance of Dnmt3a in the NAc in regulating cellular and behavioral plasticity to emotional stimuli.

引用

页码：1137 / U141

页数：9

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