TRPV1 Regulates Stress Responses through HDAC2

Abstract

Summary: 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. : Wang et al. show that Trpv1−/− mice are more stress resilient than control mice following chronic unpredictable stress and these are associated with reduced histone deacetylase (HDAC) 2 expression and activity. As a consequence, HDAC2-regulated, cell-cycle- and neuroplasticity-related molecules are altered in Trpv1−/− mice. Their findings indicate that HDAC2 is a molecular link between TRPV1 activity and stress responses. Keywords: TRPV1, behavior, depression, stress, HDAC2, GR, hippocampus