Epigenetic status of Gdnf in the ventral striatum determines susceptibility and adaptation to daily stressful events

Neuron. 2011 Jan 27;69(2):359-72. doi: 10.1016/j.neuron.2010.12.023.


Stressful events during adulthood are potent adverse environmental factors that can predispose individuals to psychiatric disorders, including depression; however, many individuals exposed to stressful events can adapt and function normally. While stress vulnerability may influence depression, the molecular mechanisms underlying the susceptibility and adaptation to chronic stress within the brain are poorly understood. In this study, two genetically distinct mouse strains that exhibit different behavioral responses to chronic stress were used to demonstrate how the differential epigenetic status of the glial cell-derived neurotrophic factor (Gdnf) gene in the ventral striatum modulates susceptibility and adaptation to chronic stress. Our results suggest that the histone modifications and DNA methylation of the Gdnf promoter have crucial roles in the control of behavioral responses to chronic stress. Our data provide insights into these mechanisms, suggesting that epigenetic modifications of Gdnf, along with genetic and environmental factors, contribute to behavioral responses to stress.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptation, Biological
  • Animals
  • Basal Ganglia / cytology
  • Basal Ganglia / physiology*
  • Behavior, Animal / physiology
  • DNA Methylation
  • Depression / drug therapy
  • Depression / physiopathology
  • Epigenesis, Genetic*
  • Glial Cell Line-Derived Neurotrophic Factor / genetics*
  • Glial Cell Line-Derived Neurotrophic Factor / metabolism*
  • Histone Deacetylase 2 / metabolism
  • Histone Deacetylase Inhibitors / metabolism
  • Histone Deacetylase Inhibitors / therapeutic use
  • Histones / metabolism
  • Hydroxamic Acids / metabolism
  • Hydroxamic Acids / therapeutic use
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Promoter Regions, Genetic
  • Stress, Psychological / genetics*
  • Vorinostat


  • Glial Cell Line-Derived Neurotrophic Factor
  • Histone Deacetylase Inhibitors
  • Histones
  • Hydroxamic Acids
  • Vorinostat
  • Histone Deacetylase 2