Dnmt3a regulates emotional behavior and spine plasticity in the nucleus accumbens

By Q. LaPlant, V. Vialou, H. Covington, Dani Dumitriu, Jian Feng, Brandon L Warren, I. Maze, D. Dietz, Emily L. Watts, S. D. Iñiguez and 17 more. Nature Neuroscience, 2010

596 citations recorded by the source corpus.

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.

Subfields: Molecular Biology, Pediatrics, Perinatology and Child Health, Pharmacology

View Paper: https://www.semanticscholar.org/paper/b1897c9cfc880421fa89b986867247d4ec6fab01

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Molecular Biology

1. Hao Wu
2. Yi Zhang
3. Alfred J. Robison
4. E. Nestler
5. G. Fan
6. Lisa D. Moore
7. Thuc M. Le
8. G. Koob

In Pediatrics, Perinatology and Child Health

1. Yi Zhang
2. Hao Wu

In Pharmacology

1. E. Nestler

Citations in the corpus

• Transcriptional and Epigenetic Mechanisms of Addiction (2011, background): “Repeated cocaine administration dynamically regulates DNMT3A expression in the mouse NAc, with decreases seen during early phases of withdrawal and sustained increases seen at later time point”
• Mechanisms and functions of Tet protein-mediated 5-methylcytosine oxidation. (2011, background): “…development and activity-dependent DNA demethylation Brain-specific deletion of DNA methyltransferases results in premature death, neural developmental defects, and impaired neuronal functions (Fan et al. 2001, 2005; Nguyen et al. 2007; J Feng et al. 2010; LaPlant et al. 2010; Wu et al. 2010).”
• DNA Methylation and Its Basic Function (2013, background): “Cocaine usage modulates Dnmt3a expression within the nucleus accumbens and enhances spine formation (LaPlant et al, 2010).”
• Reversing DNA Methylation: Mechanisms, Genomics, and Biological Functions (2014, unknown): “…the nervous system results in neurodevelopmental deficits and impaired neuronal functions (Fan et al., 2001; Fan et al., 2005; Feng et al., 2010a; LaPlant et al., 2010; Nguyen et al., 2007; Wu et al., 2010), suggesting that precise control of DNA methylation pattern is required for proper brain…”