G protein-coupled receptor 75 mediates depression-like behaviors and HPA axis hyperactivity through an excitatory arcuate-paraventricular nucleus circuit - PubMed
4 hours ago
- #GPR75
- #HPA axis
- #depression
- GPR75, a metabolic sensor, is upregulated in arcuate nucleus glutamatergic neurons in depression models.
- Knockout or inhibition of GPR75 in these neurons produces antidepressant effects and normalizes HPA axis function.
- GPR75 signaling enhances calcium release and neuronal excitability via the Gαq-PLCβ-IP3R1 pathway, increasing glutamate release in the PVN.
- Activation of the arcuate nucleus-PVN circuit promotes depression-like behaviors, while its inhibition has antidepressant effects.
- GPR75 in arcuate neurons is identified as a key mediator of depression and a potential target for new antidepressants.