Serotonergic neuron-glioma interactions drive high-grade glioma pathophysiology.

ABSTRACT: High-grade gliomas are lethal brain cancers that are powerfully regulated by glutamatergic neurons through activity-dependent paracrine factors and functional neuron-to-glioma synapses. Here, we report that serotonergic neurons promote the proliferation of high-grade gliomas throughout the brain. Serotonergic neuronal activity drives circuit-specific increases in high-grade glioma proliferation, calcium transients, and reduced survival. This growth-promoting effect is chiefly mediated by activation of the serotonin (5-hydroxytryptamine; 5HT) receptor 5HT_2A on glioma cells. Knock out or pharmacological blockade of 5HT_2A receptors in glioma abrogated the glioma growth-promoting effects of serotonergic neuronal activity, while serotonergic psychedelic drugs robustly prom

SUBMITTER: Drexler R 

PROVIDER: S-EPMC12715541 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature