CNSC-17. GLIOMA SYNAPSES RECRUIT MECHANISMS OF ADAPTIVE PLASTICITY

Abstract The nervous system plays an increasingly appreciated role in the regulation of cancer. In malignant gliomas, neuronal activity drives tumor progression not only through paracrine signaling factors such as neuroligin-3 and brain-derived neurotrophic factor (BDNF), but also electrophysiologically functional neuron-to-glioma synapses. Malignant synapses are mediated by calcium-permeable AMPA (α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid) receptors both pediatric adult high-grade consequent depolarization glioma cell membrane proliferation. exhibits plasticity synaptic connectivity strength, contributing to neural circuit form functions. health, one that promotes strength is activity-regulated secretion neurotrophin BDNF. Here, we show exhibit similar regulated BDNF-TrkB (tropomyosin receptor kinase B) signaling. Signaling TrkB, BDNF trafficking membrane, resulting increased amplitude glutamate-evoked currents cells. This potentiation shares mechanistic features with long-term (LTP) thought contribute memory learning healthy brain. regulates number Abrogation from brain microenvironment or loss TrkB human cells exerts growth inhibitory effects vivo neuron:glioma co-cultures cannot be explained classical alone. Blocking genetically pharmacologically abrogates these on substantially prolongs survival xenograft models glioblastoma diffuse intrinsic pontine (DIPG). Taken together, findings indicate augments progression. While targeting Trk presently being explored for NTRK-fusion tumors, may represent important therapeutic target NTRK2 wildtype gliomas.