CRF receptor 1 regulates anxiety behavior via sensitization of 5-HT2 receptor signaling

Abstract

Stress and anxiety disorders are risk factors for depression and these behaviours are modulated by corticotropin releasing factor (CRFR1) and serotonin (5-HT2R) receptors. However, the potential behavioral and cellular interaction between these two receptors is unclear. Here, we showed that pre-administration of CRF into the prefrontal cortex of mice sensitized 5-HT2R-mediated anxiety behaviours in response to 2,5-dimethoxy-4-iodoamphetamine. In both heterologous cell cultures and mouse cortical neurons, the activation of CRFR1 also sensitized 5-HT2 receptor-mediated inositol phosphate formation. CRFR1-mediated increases in 5-HT2R signaling were dependent upon receptor internalization and receptor recycling via rapid recycling endosomes resulting in increased cell surface 5-HT2R expression. The sensitization of 5-HT2R signaling by CRFR1 required intact PDZ domain binding motifs at the end of the C-terminal tails of both receptor types. These data reveal a novel mechanism by which CRF, a peptide known to be released by stress, sensitized anxiety-related behaviour via sensitization of 5-HT2R signaling.

Uranium modifies or not behavior and antioxidant status in the hippocampus of rats exposed since birth

“…These unexpected findings suggest decreased susceptibility to depressive-like behavior. An interaction on the molecular level has been demonstrated between corticoreleasing factor and serotonin receptors in the presence of anxiety-like behavior (Magalhaes et al, 2010) and could cause abnormal brain signals that could have an effect on depressive-like behavior. This reduction in depressivelike behavior might thus be related, directly or indirectly, to the increase of anxiety.…”

Nanoparticle-mediated signaling endosome localization regulates growth cone motility and neurite growth

“…These fMNP signaling endosomes are similar in size, transported at rates similar to Trk signaling endosomes in PC12 cells (30) and cortical neurons (31), and their transport did not affect growth cone motility or neurite growth rate on their own. Because signaling endosome dysfunction is linked to numerous nervous system diseases (19)(20)(21), fMNP signaling endosome studies may provide insight into targeting nanotherapeutics by identifying cargo-or domain-specific adaptor and motor proteins (32), and by identifying the effects nanoconjugation have on the endocytosis and trafficking of antireceptor agonist antibodies (33) that may impact nanotherapeutic efficacy.…”

“…These signaling endosomes signal persistently during retrograde (12) and anterograde (13,14) transport in axons or dendrites (15,16) directing neurite growth, survival, and cell migration (17,18). Signaling endosomes are critical long-range communication links used by neurons in the central and peripheral nervous system during development and regeneration (17), whose dysfunction is linked to nervous system disorders (19)(20)(21). Therefore, studying signaling endosome localization and related functions in regulating neurite growth is vital.…”

The Presynaptic Component of the Serotonergic System is Required for Clozapine's Efficacy

“…Rabbit polyclonal anti-5-HT 2A receptor antibody (Neuromics, Edina, MN) was used in a 1 : 500 dilution for 12 h at 4 1C for measurement of 5-HT 2A receptor protein. We have previously verified the specificity of the anti-5-HT 2A receptor antibody using 5-HT 2A WT and KO mice cortex tissue by immunoblotting (Magalhaes et al, 2010) Head-Twitch Response As previously detailed , mice were injected i.p. with 0.5-5.0 mg/kg of DOI.…”