Glioma-induced peritumoral hyperexcitability in a pediatric glioma model.

Autor: Chaunsali L; Molecular and Cellular Biology Graduate Program, School of Neuroscience, Virginia Tech, Blacksburg, VA, USA., Tewari BP; Fralin Biomedical Research Institute, Glial Biology in Health, Disease and Cancer, Virginia Tech, Roanoke, VA, USA., Gallucci A; Fralin Biomedical Research Institute, Translational Biology, Medicine and Health, Virginia Tech, Roanoke, VA, USA., Thompson EG; Department of Neurobiology, Johns Hopkins University, Baltimore, MD, USA., Savoia A; Animal and Poultry Sciences, Virginia Tech, Blacksburg, VA, USA., Feld N; School of Medicine, Virginia Commonwealth University, Richmond, VA, USA., Campbell SL; Molecular and Cellular Biology Graduate Program, School of Neuroscience, Virginia Tech, Blacksburg, VA, USA.; Fralin Biomedical Research Institute, Glial Biology in Health, Disease and Cancer, Virginia Tech, Roanoke, VA, USA.; Animal and Poultry Sciences, Virginia Tech, Blacksburg, VA, USA.
Jazyk: angličtina
Zdroj: Physiological reports [Physiol Rep] 2020 Oct; Vol. 8 (19), pp. e14567.
DOI: 10.14814/phy2.14567
Abstrakt: Epileptic seizures are among the most common presenting symptom in patients with glioma. The etiology of glioma-related seizures is complex and not completely understood. Studies using adult glioma patient tissue and adult glioma mouse models, show that neurons adjacent to the tumor mass, peritumoral neurons, are hyperexcitable and contribute to seizures. Although it is established that there are phenotypic and genotypic distinctions in gliomas from adult and pediatric patients, it is unknown whether these established differences in pediatric glioma biology and the microenvironment in which these glioma cells harbor, the developing brain, differentially impacts surrounding neurons. In the present study, we examine the effect of patient-derived pediatric glioma cells on the function of peritumoral neurons using two pediatric glioma models. Pediatric glioma cells were intracranially injected into the cerebrum of postnatal days 2 and 3 (p2/3) mouse pups for 7 days. Electrophysiological recordings showed that cortical layer 2/3 peritumoral neurons exhibited significant differences in their intrinsic properties compared to those of sham control neurons. Peritumoral neurons fired significantly more action potentials in response to smaller current injection and exhibited a depolarization block in response to higher current injection. The threshold for eliciting an action potential and pharmacologically induced epileptiform activity was lower in peritumoral neurons compared to sham. Our findings suggest that pediatric glioma cells increase excitability in the developing peritumoral neurons by exhibiting early onset of depolarization block, which was not previously observed in adult glioma peritumoral neurons.
(© 2020 The Authors. Physiological Reports published by Wiley Periodicals LLC on behalf of The Physiological Society and the American Physiological Society.)
Databáze: MEDLINE
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