Resilience to social stress coincides with functional DNA methylation of the Crf gene in adult mice

Nat Neurosci. 2010 Nov;13(11):1351-3. doi: 10.1038/nn.2642. Epub 2010 Oct 3.

Abstract

DNA methylation regulates gene transcription and has been suggested to encode psychopathologies derived from early life stress. We found that methylation regulated the expression of the Crf (also known as Crh) gene and that chronic social stress in adult mice induced long-term demethylation of this genomic region. Demethylation was observed only in the subset of defeated mice that displayed social avoidance and site-specific knockdown of Crf attenuated the stress-induced social avoidance.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Analysis of Variance
  • Animals
  • Antidepressive Agents, Tricyclic / therapeutic use
  • Avoidance Learning
  • Azacitidine / analogs & derivatives
  • Azacitidine / pharmacology
  • Cell Line, Tumor
  • Corticotropin-Releasing Hormone / deficiency
  • Corticotropin-Releasing Hormone / genetics*
  • Corticotropin-Releasing Hormone / metabolism
  • Cyclic AMP / pharmacology
  • DNA Methylation* / drug effects
  • Decitabine
  • Enzyme Inhibitors / pharmacology
  • Gene Expression Regulation / drug effects
  • Gene Expression Regulation / physiology*
  • Genetic Vectors / physiology
  • Green Fluorescent Proteins / genetics
  • Imipramine / therapeutic use
  • Injections, Intraventricular / methods
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Microdissection / methods
  • Naphthalenes
  • Neuroblastoma
  • Neurons / drug effects
  • Oxepins
  • Paraventricular Hypothalamic Nucleus / cytology
  • Paraventricular Hypothalamic Nucleus / drug effects
  • RNA Interference / physiology
  • RNA, Messenger / metabolism
  • Stress, Psychological / drug therapy*
  • Stress, Psychological / genetics*

Substances

  • 1-phenyl-1,4-epoxy-1H,4H-naphtho(1,8-de)(1,2)dioxepin
  • Antidepressive Agents, Tricyclic
  • Enzyme Inhibitors
  • Naphthalenes
  • Oxepins
  • RNA, Messenger
  • Green Fluorescent Proteins
  • Decitabine
  • Corticotropin-Releasing Hormone
  • Cyclic AMP
  • Azacitidine
  • Imipramine