Dnmt3a in the medial prefrontal cortex regulates anxiety-like behavior in adult mice

Evan Elliott, Sharon Manashirov, Raaya Zwang, Shosh Gil, Michael Tsoory, Yair Shemesh, Alon Chen

Research output: Contribution to journalArticlepeer-review


Recently, it has been suggested that alterations in DNA methylation mediate the molecular changes and psychopathologies that can occur following trauma. Despite the abundance of DNA methyltransferases (Dnmts) in the brain, which are responsible for catalyzing DNA methylation, their roles in behavioral regulation and in response to stressful challenges remain poorly understood. Here, we demonstrate that adult mice which underwent chronic social defeat stress (CSDS) displayed elevated anxiety-like behavior that was accompanied by a reduction in medial prefrontal cortex (mPFC)-DNA methyltransferase 3a (Dnmt3a) mRNA levels and a subsequent decrease in mPFCglobal DNA methylation. To explore the role of mPFC-Dnmt3a in mediating the behavioral responses to stressful challenges we established lentiviral-based mouse models that express lower (knockdown) or higher (overexpression) levels of Dnmt3a specifically within the mPFC. Nonstressed mice injected with knockdown Dnmt3a lentiviruses specifically into the mPFC displayed the same anxiogenic phenotype as the CSDS mice, whereas overexpression of Dnmt3a induced an opposite, anxiolytic, effect in wild-type mice. In addition, overexpression of Dnmt3a in the mPFC of CSDS mice attenuated stress-induced anxiety. Our results indicate a central role for mPFCDnmt3a as a mediator of stress-induced anxiety.

Original languageEnglish
Pages (from-to)730-740
Number of pages11
JournalJournal of Neuroscience
Issue number3
StatePublished - 20 Jan 2016


  • Anxiety
  • DNA methyltransferases
  • Stress

All Science Journal Classification (ASJC) codes

  • Neuroscience(all)


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