TRPV1 Regulates Stress Responses through HDAC2

Cell Rep. 2017 Apr 11;19(2):401-412. doi: 10.1016/j.celrep.2017.03.050.

Abstract

Stress causes changes in neurotransmission in the brain, thereby influencing stress-induced behaviors. However, it is unclear how neurotransmission systems orchestrate stress responses at the molecular and cellular levels. Transient receptor potential vanilloid 1 (TRPV1), a non-selective cation channel involved mainly in pain sensation, affects mood and neuroplasticity in the brain, where its role is poorly understood. Here, we show that Trpv1-deficient (Trpv1-/-) mice are more stress resilient than control mice after chronic unpredictable stress. We also found that glucocorticoid receptor (GR)-mediated histone deacetylase 2 (HDAC) 2 expression and activity are reduced in the Trpv1-/- mice and that HDAC2-regulated, cell-cycle- and neuroplasticity-related molecules are altered. Hippocampal knockdown of TRPV1 had similar effects, and its behavioral effects were blocked by HDAC2 overexpression. Collectively, our findings indicate that HDAC2 is a molecular link between TRPV1 activity and stress responses.

Keywords: GR; HDAC2; TRPV1; behavior; depression; hippocampus; stress.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cells, Cultured
  • Gene Expression Regulation
  • Hippocampus / metabolism
  • Hippocampus / physiopathology
  • Histone Deacetylase 2 / biosynthesis
  • Histone Deacetylase 2 / genetics*
  • Mice
  • Mice, Knockout
  • Neuronal Plasticity / genetics*
  • Receptors, Glucocorticoid / genetics
  • Stress, Physiological / genetics*
  • TRPV Cation Channels / biosynthesis
  • TRPV Cation Channels / genetics*

Substances

  • Receptors, Glucocorticoid
  • TRPV Cation Channels
  • TRPV1 protein, mouse
  • Hdac2 protein, mouse
  • Histone Deacetylase 2