Your browser doesn't support javascript.
loading
Electrical and synaptic integration of glioma into neural circuits.
Venkatesh, Humsa S; Morishita, Wade; Geraghty, Anna C; Silverbush, Dana; Gillespie, Shawn M; Arzt, Marlene; Tam, Lydia T; Espenel, Cedric; Ponnuswami, Anitha; Ni, Lijun; Woo, Pamelyn J; Taylor, Kathryn R; Agarwal, Amit; Regev, Aviv; Brang, David; Vogel, Hannes; Hervey-Jumper, Shawn; Bergles, Dwight E; Suvà, Mario L; Malenka, Robert C; Monje, Michelle.
Affiliation
  • Venkatesh HS; Department of Neurology, Stanford University, Stanford, CA, USA.
  • Morishita W; Department of Psychiatry and Behavioral Sciences, Stanford University, Stanford, CA, USA.
  • Geraghty AC; Nancy Pritzker Laboratory, Stanford University, Stanford, CA, USA.
  • Silverbush D; Department of Neurology, Stanford University, Stanford, CA, USA.
  • Gillespie SM; Department of Pathology and Center for Cancer Research, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
  • Arzt M; Klarman Cell Observatory, Broad Institute of Harvard and MIT, Cambridge, MA, USA.
  • Tam LT; Broad Institute of Harvard and MIT, Cambridge, MA, USA.
  • Espenel C; Department of Neurology, Stanford University, Stanford, CA, USA.
  • Ponnuswami A; Department of Neurology, Stanford University, Stanford, CA, USA.
  • Ni L; Department of Neurology, Stanford University, Stanford, CA, USA.
  • Woo PJ; Cell Sciences Imaging Facility, Stanford University School of Medicine, Stanford, CA, USA.
  • Taylor KR; Department of Neurology, Stanford University, Stanford, CA, USA.
  • Agarwal A; Department of Neurology, Stanford University, Stanford, CA, USA.
  • Regev A; Department of Neurology, Stanford University, Stanford, CA, USA.
  • Brang D; Department of Neurology, Stanford University, Stanford, CA, USA.
  • Vogel H; Department of Neuroscience, Johns Hopkins University, Baltimore, MA, USA.
  • Hervey-Jumper S; The Chica and Heinz Schaller Research Group, Institute for Anatomy and Cell Biology, Heidelberg University, Heidelberg, Germany.
  • Bergles DE; Klarman Cell Observatory, Broad Institute of Harvard and MIT, Cambridge, MA, USA.
  • Suvà ML; Broad Institute of Harvard and MIT, Cambridge, MA, USA.
  • Malenka RC; Howard Hughes Medical Institute, Koch Institute for Integrative Cancer Research, Department of Biology, MIT, Cambridge, MA, USA.
  • Monje M; Department of Psychology, University of Michigan, Ann Arbor, MI, USA.
Nature ; 573(7775): 539-545, 2019 09.
Article in En | MEDLINE | ID: mdl-31534222
ABSTRACT
High-grade gliomas are lethal brain cancers whose progression is robustly regulated by neuronal activity. Activity-regulated release of growth factors promotes glioma growth, but this alone is insufficient to explain the effect that neuronal activity exerts on glioma progression. Here we show that neuron and glioma interactions include electrochemical communication through bona fide AMPA receptor-dependent neuron-glioma synapses. Neuronal activity also evokes non-synaptic activity-dependent potassium currents that are amplified by gap junction-mediated tumour interconnections, forming an electrically coupled network. Depolarization of glioma membranes assessed by in vivo optogenetics promotes proliferation, whereas pharmacologically or genetically blocking electrochemical signalling inhibits the growth of glioma xenografts and extends mouse survival. Emphasizing the positive feedback mechanisms by which gliomas increase neuronal excitability and thus activity-regulated glioma growth, human intraoperative electrocorticography demonstrates increased cortical excitability in the glioma-infiltrated brain. Together, these findings indicate that synaptic and electrical integration into neural circuits promotes glioma progression.
Subject(s)
Fulltext
Print
XML
PubMed Links
Search on Google

Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Brain / Electrical Synapses / Electrophysiological Phenomena / Glioma Limits: Animals / Humans Language: En Journal: Nature Year: 2019 Type: Article Affiliation country: United States
Fulltext
Print
XML
PubMed Links
Search on Google

Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Brain / Electrical Synapses / Electrophysiological Phenomena / Glioma Limits: Animals / Humans Language: En Journal: Nature Year: 2019 Type: Article Affiliation country: United States