ArticleNeuron2025
Glioma-induced alterations in excitatory neurons are reversed by mTOR inhibition.
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Article in Neuron, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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16citing papers in PubMed
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Who cites it
16 citing papers in PubMed.
- Targeting the nervous system: Mechanistic insights into neuro-tumor communication and therapeutic opportunities.Acta pharmaceutica Sinica. B · 2026Review
- Metabolic Reprogramming and Neurotransmitter Signaling Co-Option in the Glioma Immune Microenvironment: Dual-Axis Regulation of Immunosuppression.Biomolecules · 2026Review
- Transsynaptic tracing techniques to interrogate neuronal connectivity of glioblastomas.Nature protocols · 2026Review
- IDH-mutant inhibitors enhance the sensitivity of IDH1-mutant gliomas to cysteine-methionine deprivation and ferroptosis.bioRxiv : the preprint server for biology · 2026Article
- Nested ecosystems theory for conceptualizing brain tumors.Disease models & mechanisms · 2026Review
- Crosstalk in the brain tumor microenvironment: mechanisms, therapeutic strategies, and clinical advances.Military Medical Research · 2026Review
- Advancing glioblastoma research by establishing a whole brain slice model.Frontiers in oncology · 2026Article
- Dysregulated Microglial Synaptic Engulfment in Diffuse Midline Glioma.bioRxiv : the preprint server for biology · 2025Article
- Connectomics in brain tumor surgery: large-scale clinical feasibility and hypothesis-generating tractometry findings.Journal of neuro-oncology · 2025Article
- Aberrant neural activity in the peritumoral cortex underlies the progression of tumor-associated seizures.Nature communications · 2025Article
- Integrating of Machine Learning to Characterize Tumor-Infiltrating Immune Cell-Related Signature for Enhancing Prognosis for Glioma Patients.Biological procedures online · 2025Article
- Small cell lung cancer induces synaptic scaling to alter neuronal excitability.Communications biology · 2025Article
- The Role of mTOR Signaling in Tumor-Induced Alterations to Neuronal Function in Diffusely Infiltrating Glioma.Biomedicines · 2025Review
- The excitatory milieu in glioma: Mechanisms and therapeutic avenues.Neuro-oncology · 2025Review
- Aperiodic neural dynamics define a novel signature of glioma-induced excitation-inhibition dysregulation.bioRxiv : the preprint server for biology · 2025Article
- Seizure outcomes as an understudied metric in glioma clinical trials: A review of the ClinicalTrials.gov database.Neuro-oncology advancesReview
Corrections and comments
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Authors and funding
39 authors.
Alexander R GoldbergDepartment of Pathology and Cell Biology, Irving Cancer Research Center, Columbia University Irving Medical Center, New York, NY 10032, USA.
Athanassios DovasDepartment of Pathology and Cell Biology, Irving Cancer Research Center, Columbia University Irving Medical Center, New York, NY 10032, USA.
Daniela TorresDepartment of Pathology and Cell Biology, Irving Cancer Research Center, Columbia University Irving Medical Center, New York, NY 10032, USA.
Brianna PereiraDepartment of Pathology and Cell Biology, Irving Cancer Research Center, Columbia University Irving Medical Center, New York, NY 10032, USA.
Ashwin ViswanathanDepartment of Pathology and Cell Biology, Irving Cancer Research Center, Columbia University Irving Medical Center, New York, NY 10032, USA.
Sohani Das SharmaDepartment of Systems Biology, Columbia University Irving Medical Center, New York, NY 10032, USA.
Angeliki MelaDepartment of Pathology and Cell Biology, Irving Cancer Research Center, Columbia University Irving Medical Center, New York, NY 10032, USA.
Edward M MerricksDepartment of Neurology, Columbia University Irving Medical Center, New York, NY 10032, USA.
Cristina Megino-LuqueDepartment of Medicine, Division of Hematology and Oncology, The Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10027, USA.
Julie J McInvaleDepartment of Pathology and Cell Biology, Irving Cancer Research Center, Columbia University Irving Medical Center, New York, NY 10032, USA.
Markel OlabarriaDepartment of Pathology and Cell Biology, Irving Cancer Research Center, Columbia University Irving Medical Center, New York, NY 10032, USA.
Leila Abrishami ShokoohDepartment of Neurology, Columbia University Irving Medical Center, New York, NY 10032, USA.
Hanzhi T ZhaoLaboratory for Functional Optical Imaging, Zuckerman Mind Brain Behavior Institute, Departments of Biomedical Engineering and Radiology, Columbia University, New York, NY 10027, USA.
Cady ChenDepartment of Pathology and Cell Biology, Irving Cancer Research Center, Columbia University Irving Medical Center, New York, NY 10032, USA.
Corina KotidisDepartment of Neurological Surgery, Columbia University Irving Medical Center, New York, NY 10032, USA.
Peter CalvaresiDepartment of Pathology and Cell Biology, Irving Cancer Research Center, Columbia University Irving Medical Center, New York, NY 10032, USA.
Matei A BanuDepartment of Neurological Surgery, Columbia University Irving Medical Center, New York, NY 10032, USA.
Aida RazavilarDepartment of Pathology and Cell Biology, Irving Cancer Research Center, Columbia University Irving Medical Center, New York, NY 10032, USA.
Tejaswi D SudhakarDepartment of Pathology and Cell Biology, Irving Cancer Research Center, Columbia University Irving Medical Center, New York, NY 10032, USA.
Ankita SaxenaDepartment of Pathology and Cell Biology, Irving Cancer Research Center, Columbia University Irving Medical Center, New York, NY 10032, USA.
Cole ChokranDepartment of Pathology and Cell Biology, Irving Cancer Research Center, Columbia University Irving Medical Center, New York, NY 10032, USA.
Nelson HumalaDepartment of Neurological Surgery, Columbia University Irving Medical Center, New York, NY 10032, USA.
Aayushi MahajanDepartment of Neurological Surgery, Columbia University Irving Medical Center, New York, NY 10032, USA.
Weihao XuLaboratory for Functional Optical Imaging, Zuckerman Mind Brain Behavior Institute, Departments of Biomedical Engineering and Radiology, Columbia University, New York, NY 10027, USA.
Jordan B MetzDepartment of Systems Biology, Columbia University Irving Medical Center, New York, NY 10032, USA.
Eric A BushongNational Center for Microscopy and Imaging Research, University of California, San Diego, La Jolla, CA 92093, USA.
Daniela BoassaNational Center for Microscopy and Imaging Research, University of California, San Diego, La Jolla, CA 92093, USA.
Mark H EllismanNational Center for Microscopy and Imaging Research, University of California, San Diego, La Jolla, CA 92093, USA.
Elizabeth M C HillmanLaboratory for Functional Optical Imaging, Zuckerman Mind Brain Behavior Institute, Departments of Biomedical Engineering and Radiology, Columbia University, New York, NY 10027, USA.
Gunnar HargusDepartment of Pathology and Cell Biology, Irving Cancer Research Center, Columbia University Irving Medical Center, New York, NY 10032, USA.
Jose Javier Bravo-CorderoDepartment of Medicine, Division of Hematology and Oncology, The Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10027, USA.
Guy M McKhannDepartment of Neurological Surgery, Columbia University Irving Medical Center, New York, NY 10032, USA.
Brian J A GillDepartment of Neurological Surgery, Columbia University Irving Medical Center, New York, NY 10032, USA.
Steven S RosenfeldDepartment of Cancer Biology, Mayo Clinic, Jacksonville, FL 32224, USA.
Catherine A SchevonDepartment of Neurology, Columbia University Irving Medical Center, New York, NY 10032, USA.
Jeffrey N BruceDepartment of Neurological Surgery, Columbia University Irving Medical Center, New York, NY 10032, USA.
Peter A SimsDepartment of Systems Biology, Columbia University Irving Medical Center, New York, NY 10032, USA; Sulzberger Columbia Genome Center, Columbia University Irving Medical Center, New York, NY 10032, USA; Department of Biochemistry & Molecular Biophysics, Columbia University Irving Medical Center, New York, NY 10032, USA.
Darcy S PeterkaIrving Institute for Cancer Dynamics, Columbia University, New York, NY 10027, USA; Mortimer B. Zuckerman Mind Brain Behavior Institute, Columbia University, New York, NY 10027, USA.
Peter CanollDepartment of Pathology and Cell Biology, Irving Cancer Research Center, Columbia University Irving Medical Center, New York, NY 10032, USA; Department of Neurological Surgery, Columbia University Irving Medical Center, New York, NY 10032, USA. Electronic address: pc561@cumc.columbia.edu.
Funding
Tumor Biology and Microenvironment ProgramP30CA013696 · NCI · COLUMBIA UNIV NEW YORK MORNINGSIDE · PI Anil K Rustgi · 1985 to 2026
$115.3MTHE TISCH CANCER INSTITUTE - CANCER CENTER SUPPORT GRANTP30CA196521 · NCI · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI Ramon E Parsons · 2015 to 2026
$35.4MOutreach CoreU54CA274504 · NCI · MAYO CLINIC ARIZONA · PI Kristin R Swanson · 2023 to 2026
$8.6MMedical Scientist Training ProgramT32GM145440 · NIGMS · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI STEVEN L REINER · 2022 to 2026
$7.3MSeizure localization in humans: the effect of inhibitory surround on the EEGR01NS084142 · NINDS · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI SCHEVON, CATHERINE A · 2013 to 2022
$6.0MNational Center for Microscopy and Imaging Research: A BRAIN Technology Integration and Dissemination ResourceU24NS120055 · NINDS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI ELLISMAN, MARK H · 2021 to 2025
$5.4MIn-vivo optical imaging of neurovascular coupling and cerebral metabolismR01NS063226 · NINDS · COLUMBIA UNIV NEW YORK MORNINGSIDE · PI HILLMAN, ELIZABETH M. C. · 2008 to 2019
$3.5MTargeting Go and Grow in GlioblastomaR01NS118513 · NINDS · MAYO CLINIC JACKSONVILLE · PI CANOLL, PETER, KENCHAPPA, RAJAPPA · 2020 to 2024
$2.8MDefining the role of type III collagen and the collagen-binding receptor DDR1 in metastatic dormancyR01CA244780 · NCI · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI BRAVO-CORDERO, JOSE JAVIER · 2020 to 2024
$1.9MElucidating the Role of Microglia and Neurotrophin Receptor p75 on Neuronal Degeneration in Frontotemporal DementiaK08NS116166 · NINDS · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI HARGUS, GUNNAR · 2021 to 2025
$968kMultidisciplinary Training in Gastrointestinal CancersT32CA285274 · NCI · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI Julian Abrams, Anil K Rustgi · 2024 to 2026
$897kIntersectional genetics-based biosensors for dormant cancer cellsR61CA278402 · NCI · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI BRAVO-CORDERO, JOSE JAVIER · 2023 to 2025
$706kNCI NIH HHS F30 CA257768NCI NIH HHS F30 CA288006NCI NIH HHS P30 CA013696NCI NIH HHS P30 CA196521NCI NIH HHS R01 CA244780NCI NIH HHS R61 CA278402NCI NIH HHS T32 CA285274NCI NIH HHS U54 CA274504NIGMS NIH HHS T32 GM145440NINDS NIH HHS K08 NS116166NINDS NIH HHS R01 NS063226NINDS NIH HHS R01 NS084142NINDS NIH HHS R01 NS118513NINDS NIH HHS R03 NS090151NINDS NIH HHS U24 NS120055
Abstract
Gliomas are aggressive neoplasms that diffusely infiltrate the brain and cause neurological symptoms, including cognitive deficits and seizures. Increased mTOR signaling has been implicated in glioma-induced neuronal hyperexcitability, but the molecular and functional consequences have not been identified. Here, we show three types of changes in tumor-associated neurons: (1) downregulation of transcripts encoding excitatory and inhibitory postsynaptic proteins and dendritic spine development and upregulation of cytoskeletal transcripts via neuron-specific profiling of ribosome-bound mRNA, (2) marked decreases in dendritic spine density via light and electron microscopy, and (3) progressive functional alterations leading to neuronal hyperexcitability via in vivo calcium imaging. A single acute dose of AZD8055, a combined mTORC1/2 inhibitor, reversed these tumor-induced changes. These findings reveal mTOR-driven pathological plasticity in neurons at the infiltrative margin of glioma and suggest new strategies for treating glioma-associated neurological symptoms.
Indexed as
Brain NeoplasmsGliomaMTOR InhibitorsNeuronsTOR Serine-Threonine KinasesAnimalsDendritic SpinesMiceMorpholines(5-(2,4-bis((3S)-3-methylmorpholin-4-yl)pyrido(2,3-d)pyrimidin-7-yl)-2-methoxyphenyl)methanolMorpholinesMTOR InhibitorsTOR Serine-Threonine Kinasesalterations in neuronal activitybrain tumor microenvironmentbrain tumorsdendritic spinesexcitatory neuronsgliomaglioma-associated neuronal alterationsglioma-induced plasticityglioma microenvironmentmTOR inhibitionneuronal hyperexcitability
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