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Updated: Jan 29, 2026
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Co-culture of Glutamatergic Neurons and Pediatric High-Grade Glioma Cells Into Microfluidic Devices to Assess Electrical Interactions
Published on: November 17, 2021
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Neuron-Glioma Synapses in Tumor Progression
Cristina Cueto-Ureña1, María Jesús Ramírez-Expósito1, José Manuel Martínez-Martos1
1Experimental and Clinical Physiopathology Research Group CTS-1039, Department of Health Sciences, School of Health Sciences, University of Jaén, E23071 Jaén, Spain.
Biomedicines
|January 28, 2026
Summary
Glioma cells form functional synapses with neurons, driving tumor growth and treatment resistance. Targeting these tumor cell connections, particularly AMPA receptors and glutamate signaling, offers new therapeutic strategies for brain tumors.
Area of Science:
- Neuro-oncology
- Cancer biology
- Molecular neuroscience
Background:
- Gliomas are aggressive primary brain tumors with limited treatment options.
- Gliomas are now understood to integrate into neural circuits, forming functional synapses with neurons.
Purpose of the Study:
- To investigate the synaptic and paracrine interactions between glioma cells and neurons.
- To explore the role of these interactions in tumor growth, invasion, and treatment resistance.
Main Methods:
- Ultrastructural studies to identify synaptic components.
- Electrophysiological recordings to detect synaptic currents in tumor cells.
- Analysis of tumor microtubules (TMs) and their associated receptors (e.g., AMPA receptors).
Main Results:
- Glioma cells form authentic electrochemical synapses with neurons, utilizing structures like tumor microtubules (TMs).
- These synapses involve glutamate release from neurons and gliomas, leading to excitotoxicity and a pro-tumorigenic microenvironment.
- Altered chloride homeostasis in some gliomas promotes growth via depolarizing GABAergic signaling.
- High functional connectivity within gliomas correlates with reduced patient survival.
Conclusions:
- Glioma-neuron and glioma-glioma synaptic interactions are critical drivers of tumor progression and therapeutic resistance.
- Targeting synaptic components, such as AMPA receptors and glutamate pathways, and chloride homeostasis presents promising therapeutic avenues.
- Developing therapies like AMPA receptor antagonists and glutamate release modulators may improve outcomes for glioma patients.
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