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HGG-02. NEUROPHYSIOLOGICAL SMALL MOLECULE SCREEN TO TARGET NEURON-GLIOMA INTERACTIONS IN PEDIATRIC HIGH-GRADE GLIOMAS
Neurons stimulate glioma growth via synaptic and paracrine signaling mechanisms. We recently demonstrated that neurons form AMPA receptor-dependent synapses with glioma cells, and that neuronal activity also induces potassium-evoked currents that are amplified by gap junctions coupling glioma cells....
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Oxford University Press
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8168233/ http://dx.doi.org/10.1093/neuonc/noab090.068 |
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author | Rogawski, David Mulinyawe, Sara Thomas, Craig Monje, Michelle |
author_facet | Rogawski, David Mulinyawe, Sara Thomas, Craig Monje, Michelle |
author_sort | Rogawski, David |
collection | PubMed |
description | Neurons stimulate glioma growth via synaptic and paracrine signaling mechanisms. We recently demonstrated that neurons form AMPA receptor-dependent synapses with glioma cells, and that neuronal activity also induces potassium-evoked currents that are amplified by gap junctions coupling glioma cells. However, our understanding of the neurotransmitters, receptors, and ion channels participating in neuron-glioma signaling remains incomplete. We have recently developed a high-throughput neuron-glioma co-culture strategy to screen small molecules for agents that may disrupt neuron-glioma signaling. Glioma cell proliferation is increased tenfold when cultured together with neurons; this robust biological effect can be probed in a targeted screen of compounds influencing neurotransmitter receptors and ion channels. The neurophysiological small molecule library used was curated to include approved anti-epileptics, neuroleptics, and antidepressants, as well as a variety of other compounds acting on different neurotransmitter types and ion channels. Hits from the primary screen were run through a counter-screen using glioma cells grown alone without neurons, to identify compounds that specifically affect neuron-glioma interactions. Correlation of the screening results with drug mechanisms of action will allow us to map out the key neurotransmitter pathways regulating glioma growth, which can be further validated using genetic and in vivo experiments. Drugs identified in this glioma neuroscience screen may be readily translated into much-needed therapeutics for children with high-grade glioma. |
format | Online Article Text |
id | pubmed-8168233 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Oxford University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-81682332021-06-02 HGG-02. NEUROPHYSIOLOGICAL SMALL MOLECULE SCREEN TO TARGET NEURON-GLIOMA INTERACTIONS IN PEDIATRIC HIGH-GRADE GLIOMAS Rogawski, David Mulinyawe, Sara Thomas, Craig Monje, Michelle Neuro Oncol High Grade Gliomas Neurons stimulate glioma growth via synaptic and paracrine signaling mechanisms. We recently demonstrated that neurons form AMPA receptor-dependent synapses with glioma cells, and that neuronal activity also induces potassium-evoked currents that are amplified by gap junctions coupling glioma cells. However, our understanding of the neurotransmitters, receptors, and ion channels participating in neuron-glioma signaling remains incomplete. We have recently developed a high-throughput neuron-glioma co-culture strategy to screen small molecules for agents that may disrupt neuron-glioma signaling. Glioma cell proliferation is increased tenfold when cultured together with neurons; this robust biological effect can be probed in a targeted screen of compounds influencing neurotransmitter receptors and ion channels. The neurophysiological small molecule library used was curated to include approved anti-epileptics, neuroleptics, and antidepressants, as well as a variety of other compounds acting on different neurotransmitter types and ion channels. Hits from the primary screen were run through a counter-screen using glioma cells grown alone without neurons, to identify compounds that specifically affect neuron-glioma interactions. Correlation of the screening results with drug mechanisms of action will allow us to map out the key neurotransmitter pathways regulating glioma growth, which can be further validated using genetic and in vivo experiments. Drugs identified in this glioma neuroscience screen may be readily translated into much-needed therapeutics for children with high-grade glioma. Oxford University Press 2021-06-01 /pmc/articles/PMC8168233/ http://dx.doi.org/10.1093/neuonc/noab090.068 Text en © The Author(s) 2021. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com. https://creativecommons.org/licenses/by-nc/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/ (https://creativecommons.org/licenses/by-nc/4.0/) ), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com |
spellingShingle | High Grade Gliomas Rogawski, David Mulinyawe, Sara Thomas, Craig Monje, Michelle HGG-02. NEUROPHYSIOLOGICAL SMALL MOLECULE SCREEN TO TARGET NEURON-GLIOMA INTERACTIONS IN PEDIATRIC HIGH-GRADE GLIOMAS |
title | HGG-02. NEUROPHYSIOLOGICAL SMALL MOLECULE SCREEN TO TARGET NEURON-GLIOMA INTERACTIONS IN PEDIATRIC HIGH-GRADE GLIOMAS |
title_full | HGG-02. NEUROPHYSIOLOGICAL SMALL MOLECULE SCREEN TO TARGET NEURON-GLIOMA INTERACTIONS IN PEDIATRIC HIGH-GRADE GLIOMAS |
title_fullStr | HGG-02. NEUROPHYSIOLOGICAL SMALL MOLECULE SCREEN TO TARGET NEURON-GLIOMA INTERACTIONS IN PEDIATRIC HIGH-GRADE GLIOMAS |
title_full_unstemmed | HGG-02. NEUROPHYSIOLOGICAL SMALL MOLECULE SCREEN TO TARGET NEURON-GLIOMA INTERACTIONS IN PEDIATRIC HIGH-GRADE GLIOMAS |
title_short | HGG-02. NEUROPHYSIOLOGICAL SMALL MOLECULE SCREEN TO TARGET NEURON-GLIOMA INTERACTIONS IN PEDIATRIC HIGH-GRADE GLIOMAS |
title_sort | hgg-02. neurophysiological small molecule screen to target neuron-glioma interactions in pediatric high-grade gliomas |
topic | High Grade Gliomas |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8168233/ http://dx.doi.org/10.1093/neuonc/noab090.068 |
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