Tryptamine from wake-active monoaminergic neurons regulates sleep homeostasis - PubMed
6 hours ago
- #sleep homeostasis
- #tryptamine
- #GPR139
- Tryptamine (TrpA) levels in cerebrospinal fluid track homeostatic sleep pressure in mice and pigs, correlating with physical activity independent of light-dark cycles.
- A ratiometric fluorescent sensor revealed that TrpA is produced by wake-active monoaminergic nuclei in the diencephalon and brainstem and secreted activity-dependently.
- Released TrpA binds to G-protein-coupled receptor 139 (GPR139) in the hypothalamic preoptic area, enhancing neuronal excitability to promote sleep.
- TrpA-GPR139 signaling is essential for homeostatic sleep rebound, and GPR139 agonists increase sleep duration and quality.
- TrpA is identified as a signal for sleep homeostasis, and GPR139 emerges as a druggable target for sleep regulation.