Electrical and synaptic integration of glioma into neural circuits

被引：842

作者：

Venkatesh, Humsa S. ^{[1
]}

Morishita, Wade ^{[2
,3
]}

Geraghty, Anna C. ^{[1
]}

Silverbush, Dana ^{[4
,5
,6
]}

Gillespie, Shawn M. ^{[1
]}

Arzt, Marlene ^{[1
]}

Tam, Lydia T. ^{[1
]}

Espenel, Cedric ^{[7
]}

Ponnuswami, Anitha ^{[1
]}

Ni, Lijun ^{[1
]}

Woo, Pamelyn J. ^{[1
]}

Taylor, Kathryn R. ^{[1
]}

Agarwal, Amit ^{[8
,15
]}

Regev, Aviv ^{[6
,9
]}

Brang, David ^{[10
]}

Vogel, Hannes ^{[1
,11
,12
]}

Hervey-Jumper, Shawn ^{[13
]}

Bergles, Dwight E. ^{[8
]}

Suva, Mario L. ^{[6
]}

Malenka, Robert C. ^{[2
]}

Monje, Michelle ^{[1
,2
,11
,12
,14
]}

机构：

[1] Stanford Univ, Dept Neurol, Stanford, CA 94305 USA

[2] Stanford Univ, Dept Psychiat & Behav Sci, Stanford, CA 94305 USA

[3] Stanford Univ, Nancy Pritzker Lab, Stanford, CA 94305 USA

[4] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA

[5] Massachusetts Gen Hosp, Ctr Canc Res, Boston, MA 02114 USA

[6] Broad Inst Harvard & MIT, Cambridge, MA USA

[7] Stanford Univ, Cell Sci Imaging Facil, Sch Med, Stanford, CA USA

[8] Johns Hopkins Univ, Dept Neurosci, Baltimore, MA USA

[9] MIT, Koch Inst Integrat Canc Res, Dept Biol, Howard Hughes Med Inst, Cambridge, MA USA

[10] Univ Michigan, Dept Psychol, 580 Union Dr, Ann Arbor, MI 48104 USA

[11] Stanford Univ, Dept Pathol, Stanford, CA 94305 USA

[12] Stanford Univ, Dept Pediat, Stanford, CA 94305 USA

[13] Univ Calif San Francisco, Dept Neurol Surg, San Francisco, CA USA

[14] Stanford Univ, Inst Stem Cell Biol & Regenerat Med, Stanford, CA 94305 USA

[15] Heidelberg Univ, Inst Anat & Cell Biol, Chica & Heinz Schaller Res Grp, Heidelberg, Germany

来源：

NATURE | 2019年 / 573卷 / 7775期

基金：

美国国家卫生研究院;

关键词：

NEURONAL-ACTIVITY; GLUTAMATE RELEASE; GAP-JUNCTIONS; RNA-SEQ; CELLS; IMAGE; ACTIVATION; GROWTH; IDENTIFICATION; PROLIFERATION;

D O I：

10.1038/s41586-019-1563-y

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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.

引用

页码：539 / +

页数：24

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