An increasing body of evidence has become available to reveal the synaptic and functional integration of glioma into the brain network, facilitating tumor progression. The novel discovery of glioma‑neuronal interactions has fundamentally challenged our understanding of this refractory disease. The present review aimed to provide an overview of how the neuronal activities function through synapses, neurotransmitters, ion channels, gap junctions, tumor microtubes and neuronal molecules to establish communications with glioma, as well as a simplified explanation of the reciprocal effects of crosstalk on neuronal pathophysiology. In addition, the current state of therapeutic avenues targeting critical factors involved in glioma‑euronal interactions is discussed and an overview of clinical trial data for further investigation is provided. Finally, newly emerging technologies, including immunomodulation, a neural stem cell‑based delivery system, optogenetics techniques and co‑culture of neuron organoids and glioma, are proposed, which may pave a way towards gaining deeper insight into both the mechanisms associated with neuron‑ and glioma‑communicating networks and the development of therapeutic strategies to target this currently lethal brain tumor.
Keywords: glioma; neuron; neurotransmitter; synapse; tumor microenvironment.