Dnmt3a regulates emotional behavior and spine plasticity in the nucleus accumbens

Quincey Laplant; Vincent Vialou; Herbert E. Covington; Dani Dumitriu; Jian Feng; Brandon L. Warren; Ian Maze; David M. Dietz; Emily L. Watts; Sergio D. Iñiguez; Ja Wook Koo; Ezekiell Mouzon; William Renthal; Fiona Hollis; Hui Wang; Michele A. Noonan; Yanhua Ren; Amelia J. Eisch; Carlos A. Bolaños; Mohamed Kabbaj; Guanghua Xiao; Rachael L. Neve; Yasmin L. Hurd; Ronald S. Oosting; Gouping Fan; John H. Morrison; Eric J. Nestler

doi:10.1038/nn.2619

Dnmt3a regulates emotional behavior and spine plasticity in the nucleus accumbens

Quincey Laplant, Vincent Vialou, Herbert E. Covington, Dani Dumitriu, Jian Feng, Brandon L. Warren, Ian Maze, David M. Dietz, Emily L. Watts, Sergio D. Iñiguez, Ja Wook Koo, Ezekiell Mouzon, William Renthal, Fiona Hollis, Hui Wang, Michele A. Noonan, Yanhua Ren, Amelia J. Eisch, Carlos A. Bolaños, Mohamed KabbajGuanghua Xiao, Rachael L. Neve, Yasmin L. Hurd, Ronald S. Oosting, Gouping Fan, John H. Morrison, Eric J. Nestler

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484 Scopus citations

Abstract

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.

Original language	English
Pages (from-to)	1137-1143
Number of pages	7
Journal	Nature Neuroscience
Volume	13
Issue number	9
DOIs	https://doi.org/10.1038/nn.2619
State	Published - Sep 2010

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Laplant, Q., Vialou, V., Covington, H. E., Dumitriu, D., Feng, J., Warren, B. L., Maze, I., Dietz, D. M., Watts, E. L., Iñiguez, S. D., Koo, J. W., Mouzon, E., Renthal, W., Hollis, F., Wang, H., Noonan, M. A., Ren, Y., Eisch, A. J., Bolaños, C. A., ... Nestler, E. J. (2010). Dnmt3a regulates emotional behavior and spine plasticity in the nucleus accumbens. Nature Neuroscience, 13(9), 1137-1143. https://doi.org/10.1038/nn.2619

@article{90444d43968f4224970198daf802ab18,

title = "Dnmt3a regulates emotional behavior and spine plasticity in the nucleus accumbens",

abstract = "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.",

author = "Quincey Laplant and Vincent Vialou and Covington, {Herbert E.} and Dani Dumitriu and Jian Feng and Warren, {Brandon L.} and Ian Maze and Dietz, {David M.} and Watts, {Emily L.} and I{\~n}iguez, {Sergio D.} and Koo, {Ja Wook} and Ezekiell Mouzon and William Renthal and Fiona Hollis and Hui Wang and Noonan, {Michele A.} and Yanhua Ren and Eisch, {Amelia J.} and Bola{\~n}os, {Carlos A.} and Mohamed Kabbaj and Guanghua Xiao and Neve, {Rachael L.} and Hurd, {Yasmin L.} and Oosting, {Ronald S.} and Gouping Fan and Morrison, {John H.} and Nestler, {Eric J.}",

note = "Funding Information: We thank R. Jaenisch for the generous gift of the Dnmt3a plasmid and W.G. Janssen for animal perfusions. We also thank A.J. Robison for helpful discussions and comments on the manuscript. This work was supported by grants from the National Institute on Drug Abuse and National Institute of Mental Health.",

year = "2010",

month = sep,

doi = "10.1038/nn.2619",

language = "English",

volume = "13",

pages = "1137--1143",

journal = "Nature Neuroscience",

issn = "1097-6256",

publisher = "Nature Publishing Group",

number = "9",

}

Laplant, Q, Vialou, V, Covington, HE, Dumitriu, D, Feng, J, Warren, BL, Maze, I, Dietz, DM, Watts, EL, Iñiguez, SD, Koo, JW, Mouzon, E, Renthal, W, Hollis, F, Wang, H, Noonan, MA, Ren, Y, Eisch, AJ, Bolaños, CA, Kabbaj, M, Xiao, G, Neve, RL, Hurd, YL, Oosting, RS, Fan, G, Morrison, JH & Nestler, EJ 2010, 'Dnmt3a regulates emotional behavior and spine plasticity in the nucleus accumbens', Nature Neuroscience, vol. 13, no. 9, pp. 1137-1143. https://doi.org/10.1038/nn.2619

TY - JOUR

T1 - Dnmt3a regulates emotional behavior and spine plasticity in the nucleus accumbens

AU - Laplant, Quincey

AU - Vialou, Vincent

AU - Covington, Herbert E.

AU - Dumitriu, Dani

AU - Feng, Jian

AU - Warren, Brandon L.

AU - Maze, Ian

AU - Dietz, David M.

AU - Watts, Emily L.

AU - Iñiguez, Sergio D.

AU - Koo, Ja Wook

AU - Mouzon, Ezekiell

AU - Renthal, William

AU - Hollis, Fiona

AU - Wang, Hui

AU - Noonan, Michele A.

AU - Ren, Yanhua

AU - Eisch, Amelia J.

AU - Bolaños, Carlos A.

AU - Kabbaj, Mohamed

AU - Xiao, Guanghua

AU - Neve, Rachael L.

AU - Hurd, Yasmin L.

AU - Oosting, Ronald S.

AU - Fan, Gouping

AU - Morrison, John H.

AU - Nestler, Eric J.

N1 - Funding Information: We thank R. Jaenisch for the generous gift of the Dnmt3a plasmid and W.G. Janssen for animal perfusions. We also thank A.J. Robison for helpful discussions and comments on the manuscript. This work was supported by grants from the National Institute on Drug Abuse and National Institute of Mental Health.

PY - 2010/9

Y1 - 2010/9

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=77956139754&partnerID=8YFLogxK

U2 - 10.1038/nn.2619

DO - 10.1038/nn.2619

M3 - Article

C2 - 20729844

AN - SCOPUS:77956139754

SN - 1097-6256

VL - 13

SP - 1137

EP - 1143

JO - Nature Neuroscience

JF - Nature Neuroscience

IS - 9

ER -

Dnmt3a regulates emotional behavior and spine plasticity in the nucleus accumbens

Abstract

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