New Study Uncovers How Gliomas Disrupt Brain Function and Points to Rapid Therapeutic Reversal
A new study led by Dr. Peter Canoll’s lab, in collaboration with researchers at Columbia University Irving Medical Center, Zuckerman Institute, and Irving Institute for Cancer Dynamics, along with multiple other researchers at other universities, provides novel insights into how gliomas—aggressive brain tumors—cause debilitating neurological symptoms such as seizures and cognitive impairments. Published in Neuron, the research highlights how gliomas infiltrate the brain's cortex, disrupt neuronal function, and trigger hyperexcitability, while also demonstrating a rapid, promising therapeutic approach to reversing these effects.
Using a combination of techniques and cutting-edge tools, such as in-vivo two-photon imaging, the team investigated neuronal changes in a glioma mouse model. This approach allowed for precise, real-time mapping of neuronal activity and structural changes in the brain. The study revealed that glioma-associated neurons lose critical synaptic connections, exhibit hyperexcitability, and generate epileptic discharges in response to normal sensory stimuli.
Remarkably, the research showed that an experimental drug, AZD8055, which inhibits the mTOR signaling pathway, could reverse these neuronal disruptions within just six hours of treatment. “This study not only highlights the mechanisms driving glioma-induced dysfunction but also shows that key aspects of this damage are rapidly reversible,” said Dr. Canoll.
“Besides, the novel experimental mouse model we developed provides a powerful way to study the effects of stimulus-evoked activity on glioma growth. Many researchers in the field of cancer neuroscience are interested in understanding how neuronal activity may affect tumor growth—our model provides a physiologically relevant way to directly stimulate neuronal activity in the tumor and monitor the effect on both tumor cells and neurons,” adds Dr. Canoll.
While this study relied on in-vivo two-photon imaging for its groundbreaking findings, future research is planned to leverage advanced tools, including the serial two-photon tomography system available at the Zuckerman Institute and IICD. This system, which allows researchers to image and annotate tumor biopsies with high precision, is expected to provide critical insights into neuronal alterations at the infiltrative margin of tumors. “Studies are currently underway to use this equipment in follow-up research, where we aim to investigate how tumor cells interact with neuronal structures at a deeper level,” said Dr. Canoll.
The findings also underscore the potential of mTOR inhibitors as therapeutic targets and offer a novel experimental model to study how neuronal activity influences tumor progression. This work reflects the collaborative strength of interdisciplinary research, bringing together experts in pathology, neurosurgery, neurology, systems biology, and advanced imaging technologies.
The study represents a significant step forward in understanding and addressing the devastating neurological complications of gliomas, with the potential to improve treatments and patient outcomes.