FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W4380355514> ?p ?o ?g. }

• W4380355514 endingPage "i11" @default.
• W4380355514 startingPage "i11" @default.
• W4380355514 abstract "Abstract High-grade gliomas include clinically and molecularly distinct subtypes that stratify by anatomical location into diffuse midline gliomas (DMG) such as diffuse intrinsic pontine glioma (DIPG) and hemispheric high-grade gliomas. Neuronal activity drives high-grade glioma progression both through paracrine signaling and direct neuron-to-glioma synapses. Glutamatergic, AMPA receptor-dependent synapses between neurons and malignant glioma cells have been demonstrated in both pediatric and adult high-grade gliomas, but neuron-to-glioma synapses mediated by other neurotransmitters remain largely unexplored. Using whole-cell patch clamp electrophysiology, in vivo optogenetics and patient-derived glioma xenograft models, we have now identified functional, tumor-promoting GABAergic neuron-to-glioma synapses mediated by GABAA receptors in DMGs. GABAergic input has a depolarizing effect on DMG cells due to NKCC1 expression and consequently elevated intracellular chloride concentration in DMG tumor cells. As membrane depolarization increases glioma proliferation, we find that the activity of GABAergic interneurons promotes DMG proliferation in vivo. Increasing GABA signaling with the benzodiazepine lorazepam – a positive allosteric modulator of GABAA receptors commonly administered to children with DMG for nausea or anxiety - increases GABAA receptor conductance and increases glioma proliferation in orthotopic xenograft models of DMG. Conversely, levetiracetam, an anti-epileptic drug that attenuates GABAergic neuron-to-glioma synaptic currents, reduces glioma proliferation in patient-derived DMG xenografts and extends survival of mice bearing DMG xenografts. Concordant with gene expression patterns of GABAA receptor subunit genes across subtypes of glioma, depolarizing GABAergic currents were not found in hemispheric high-grade gliomas. Accordingly, neither lorazepam nor levetiracetam influenced the growth rate of hemispheric high-grade glioma patient-derived xenograft models. Retrospective real-world clinical data are consistent with these conclusions and should be replicated in future prospective clinical studies. Taken together, these findings uncover GABAergic synaptic communication between GABAergic interneurons and DMG cells, underscoring a tumor subtype-specific mechanism of brain cancer neurophysiology with important potential implications for commonly used drugs in this disease context." @default.
• W4380355514 created "2023-06-13" @default.
• W4380355514 creator A5000044473 @default.
• W4380355514 creator A5001293585 @default.
• W4380355514 creator A5002452432 @default.
• W4380355514 creator A5007217873 @default.
• W4380355514 creator A5007576526 @default.
• W4380355514 creator A5007951242 @default.
• W4380355514 creator A5008828385 @default.
• W4380355514 creator A5014921835 @default.
• W4380355514 creator A5017343643 @default.
• W4380355514 creator A5022800990 @default.
• W4380355514 creator A5023640403 @default.
• W4380355514 creator A5032516213 @default.
• W4380355514 creator A5034712926 @default.
• W4380355514 creator A5035531169 @default.
• W4380355514 creator A5061797035 @default.
• W4380355514 creator A5061814672 @default.
• W4380355514 creator A5063472392 @default.
• W4380355514 creator A5063490406 @default.
• W4380355514 creator A5064338108 @default.
• W4380355514 creator A5073278607 @default.
• W4380355514 creator A5074640732 @default.
• W4380355514 date "2023-06-01" @default.
• W4380355514 modified "2023-10-16" @default.
• W4380355514 title "CNSC-01. GABAERGIC NEURON-TO-GLIOMA SYNAPSES IN DIFFUSE MIDLINE GLIOMAS" @default.
• W4380355514 doi "https://doi.org/10.1093/neuonc/noad073.044" @default.
• W4380355514 hasPublicationYear "2023" @default.
• W4380355514 type Work @default.
• W4380355514 citedByCount "0" @default.
• W4380355514 crossrefType "journal-article" @default.
• W4380355514 hasAuthorship W4380355514A5000044473 @default.
• W4380355514 hasAuthorship W4380355514A5001293585 @default.
• W4380355514 hasAuthorship W4380355514A5002452432 @default.
• W4380355514 hasAuthorship W4380355514A5007217873 @default.
• W4380355514 hasAuthorship W4380355514A5007576526 @default.
• W4380355514 hasAuthorship W4380355514A5007951242 @default.
• W4380355514 hasAuthorship W4380355514A5008828385 @default.
• W4380355514 hasAuthorship W4380355514A5014921835 @default.
• W4380355514 hasAuthorship W4380355514A5017343643 @default.
• W4380355514 hasAuthorship W4380355514A5022800990 @default.
• W4380355514 hasAuthorship W4380355514A5023640403 @default.
• W4380355514 hasAuthorship W4380355514A5032516213 @default.
• W4380355514 hasAuthorship W4380355514A5034712926 @default.
• W4380355514 hasAuthorship W4380355514A5035531169 @default.
• W4380355514 hasAuthorship W4380355514A5061797035 @default.
• W4380355514 hasAuthorship W4380355514A5061814672 @default.
• W4380355514 hasAuthorship W4380355514A5063472392 @default.
• W4380355514 hasAuthorship W4380355514A5063490406 @default.
• W4380355514 hasAuthorship W4380355514A5064338108 @default.
• W4380355514 hasAuthorship W4380355514A5073278607 @default.
• W4380355514 hasAuthorship W4380355514A5074640732 @default.
• W4380355514 hasBestOaLocation W43803555141 @default.
• W4380355514 hasConcept C147944092 @default.
• W4380355514 hasConcept C160268369 @default.
• W4380355514 hasConcept C168258287 @default.
• W4380355514 hasConcept C169760540 @default.
• W4380355514 hasConcept C170493617 @default.
• W4380355514 hasConcept C17077164 @default.
• W4380355514 hasConcept C185263204 @default.
• W4380355514 hasConcept C2778227246 @default.
• W4380355514 hasConcept C2778794669 @default.
• W4380355514 hasConcept C2779177108 @default.
• W4380355514 hasConcept C502942594 @default.
• W4380355514 hasConcept C55493867 @default.
• W4380355514 hasConcept C61174792 @default.
• W4380355514 hasConcept C86803240 @default.
• W4380355514 hasConceptScore W4380355514C147944092 @default.
• W4380355514 hasConceptScore W4380355514C160268369 @default.
• W4380355514 hasConceptScore W4380355514C168258287 @default.
• W4380355514 hasConceptScore W4380355514C169760540 @default.
• W4380355514 hasConceptScore W4380355514C170493617 @default.
• W4380355514 hasConceptScore W4380355514C17077164 @default.
• W4380355514 hasConceptScore W4380355514C185263204 @default.
• W4380355514 hasConceptScore W4380355514C2778227246 @default.
• W4380355514 hasConceptScore W4380355514C2778794669 @default.
• W4380355514 hasConceptScore W4380355514C2779177108 @default.
• W4380355514 hasConceptScore W4380355514C502942594 @default.
• W4380355514 hasConceptScore W4380355514C55493867 @default.
• W4380355514 hasConceptScore W4380355514C61174792 @default.
• W4380355514 hasConceptScore W4380355514C86803240 @default.
• W4380355514 hasIssue "Supplement_1" @default.
• W4380355514 hasLocation W43803555141 @default.
• W4380355514 hasOpenAccess W4380355514 @default.
• W4380355514 hasPrimaryLocation W43803555141 @default.
• W4380355514 hasRelatedWork W10615822 @default.
• W4380355514 hasRelatedWork W1926595723 @default.
• W4380355514 hasRelatedWork W1978548250 @default.
• W4380355514 hasRelatedWork W2049860992 @default.
• W4380355514 hasRelatedWork W2122787130 @default.
• W4380355514 hasRelatedWork W2901261932 @default.
• W4380355514 hasRelatedWork W2929165788 @default.
• W4380355514 hasRelatedWork W2953460237 @default.
• W4380355514 hasRelatedWork W4308735323 @default.
• W4380355514 hasRelatedWork W4380355514 @default.
• W4380355514 hasVolume "25" @default.
• W4380355514 isParatext "false" @default.
• W4380355514 isRetracted "false" @default.

• next