Dnmt3a regulates emotional behavior and spine plasticity in the nucleus accumbens.

Q. LaPlant; V. Vialou; 3.r.d. Covington HE; D. Dumitriu; J. Feng; B.L. Warren; I. Maze; D.M. Dietz; E.L. Watts; S.D. Iniguez; J.W. Koo; E. Mouzon; W. Renthal; F. Hollis; H. Wang; M.A. Noonan; Y. Ren; A.J. Eisch; C.A. Bolanos; M. Kabbaj; G. Xiao; R.L. Neve; Y.L. Hurd; R.S. Oosting; G. Fan; J.H. Morrison; E.J. Nestler

Dnmt3a regulates emotional behavior and spine plasticity in the nucleus accumbens.

Q. LaPlant, V. Vialou, 3.r.d. Covington HE, D. Dumitriu, J. Feng, B.L. Warren, I. Maze, D.M. Dietz, E.L. Watts, S.D. Iniguez, J.W. Koo, E. Mouzon, W. Renthal, F. Hollis, H. Wang, M.A. Noonan, Y. Ren, A.J. Eisch, C.A. Bolanos, M. KabbajG. Xiao, R.L. Neve, Y.L. Hurd, R.S. Oosting, G. Fan, J.H. Morrison, E.J. Nestler

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Research output: Contribution to journal › Article › Academic › peer-review

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	Undefined/Unknown
Pages (from-to)	1137-43
Number of pages	7
Journal	Nature Neuroscience
Volume	13
Issue number	9
Publication status	Published - 2010

Cite this

LaPlant, Q., Vialou, V., Covington HE, . R. D., Dumitriu, D., Feng, J., Warren, B. L., Maze, I., Dietz, D. M., Watts, E. L., Iniguez, S. D., Koo, J. W., Mouzon, E., Renthal, W., Hollis, F., Wang, H., Noonan, M. A., Ren, Y., Eisch, A. J., Bolanos, C. A., ... Nestler, E. J. (2010). Dnmt3a regulates emotional behavior and spine plasticity in the nucleus accumbens. Nature Neuroscience, 13(9), 1137-43.

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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 = "Q. LaPlant and V. Vialou and {Covington HE}, 3.r.d. and D. Dumitriu and J. Feng and B.L. Warren and I. Maze and D.M. Dietz and E.L. Watts and S.D. Iniguez and J.W. Koo and E. Mouzon and W. Renthal and F. Hollis and H. Wang and M.A. Noonan and Y. Ren and A.J. Eisch and C.A. Bolanos and M. Kabbaj and G. Xiao and R.L. Neve and Y.L. Hurd and R.S. Oosting and G. Fan and J.H. Morrison and E.J. Nestler",

year = "2010",

language = "Undefined/Unknown",

volume = "13",

pages = "1137--43",

journal = "Nature Neuroscience",

issn = "1097-6256",

publisher = "Nature Publishing Group",

number = "9",

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LaPlant, Q, Vialou, V, Covington HE, RD, Dumitriu, D, Feng, J, Warren, BL, Maze, I, Dietz, DM, Watts, EL, Iniguez, SD, Koo, JW, Mouzon, E, Renthal, W, Hollis, F, Wang, H, Noonan, MA, Ren, Y, Eisch, AJ, Bolanos, 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. 1137-43.

TY - JOUR

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

AU - LaPlant, Q.

AU - Vialou, V.

AU - Covington HE, 3.r.d.

AU - Dumitriu, D.

AU - Feng, J.

AU - Warren, B.L.

AU - Maze, I.

AU - Dietz, D.M.

AU - Watts, E.L.

AU - Iniguez, S.D.

AU - Koo, J.W.

AU - Mouzon, E.

AU - Renthal, W.

AU - Hollis, F.

AU - Wang, H.

AU - Noonan, M.A.

AU - Ren, Y.

AU - Eisch, A.J.

AU - Bolanos, C.A.

AU - Kabbaj, M.

AU - Xiao, G.

AU - Neve, R.L.

AU - Hurd, Y.L.

AU - Oosting, R.S.

AU - Fan, G.

AU - Morrison, J.H.

AU - Nestler, E.J.

PY - 2010

Y1 - 2010

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.

M3 - Article

SN - 1097-6256

VL - 13

SP - 1137

EP - 1143

JO - Nature Neuroscience

JF - Nature Neuroscience

IS - 9

ER -