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.
authors: Fishberg Department of Neuroscience, Mount Sinai School of Medicine, New York, New York, USA.
authors: Quincey
authors: Q
authors: LaPlant
authors: Vincent
authors: V
authors: Vialou
authors: Herbert E
authors: HE
authors: Covington
authors: Dani
authors: D
authors: Dumitriu
authors: Jian
authors: J
authors: Feng
authors: Brandon L
authors: BL
authors: Warren
authors: Ian
authors: I
authors: Maze
authors: David M
authors: DM
authors: Dietz
authors: Emily L
authors: EL
authors: Watts
authors: Sergio D
authors: SD
authors: Iñiguez
authors: Ja Wook
authors: JW
authors: Koo
authors: Ezekiell
authors: E
authors: Mouzon
authors: William
authors: W
authors: Renthal
authors: Fiona
authors: F
authors: Hollis
authors: Hui
authors: H
authors: Wang
authors: Michele A
authors: MA
authors: Noonan
authors: Yanhua
authors: Y
authors: Ren
authors: Amelia J
authors: AJ
authors: Eisch
authors: Carlos A
authors: CA
authors: Bolaños
authors: Mohamed
authors: M
authors: Kabbaj
authors: Guanghua
authors: G
authors: Xiao
authors: Rachael L
authors: RL
authors: Neve
authors: Yasmin L
authors: YL
authors: Hurd
authors: Ronald S
authors: RS
authors: Oosting
authors: Gouping
authors: G
authors: Fan
authors: John H
authors: JH
authors: Morrison
authors: Eric J
authors: EJ
authors: Nestler
mesh_terms: D000818:Animals; D002908:Chronic Disease; D003042:Cocaine / Q000008:administration & dosage / Q000494:pharmacology; D004248:DNA (Cytosine-5-)-Methyltransferases / Q000235:genetics / Q000378:metabolism*; D019175:DNA Methylation; D000090205:DNA Methyltransferase 3A; D049229:Dendritic Spines / Q000187:drug effects / Q000502:physiology*; D003863:Depression / Q000235:genetics / Q000378:metabolism; D004291:Dominance-Subordination; D018765:Dopamine Uptake Inhibitors / Q000008:administration & dosage / Q000494:pharmacology; D004644:Emotions / Q000502:physiology*; D005786:Gene Expression Regulation / Q000187:drug effects; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009473:Neuronal Plasticity / Q000187:drug effects / Q000502:physiology*; D009474:Neurons / Q000502:physiology; D009714:Nucleus Accumbens / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D020318:Rats, Long-Evans; D017207:Rats, Sprague-Dawley; D013315:Stress, Psychological / Q000235:genetics / Q000378:metabolism
chemical_list: C000715535:Dnmt3a protein, mouse; D018765:Dopamine Uptake Inhibitors; D004248:DNA (Cytosine-5-)-Methyltransferases; D000090205:DNA Methyltransferase 3A; D003042:Cocaine