A role for intracellular zinc in glioma alteration of neuronal chloride equilibrium.

Abstract:

:Glioma patients commonly suffer from epileptic seizures. However, the mechanisms of glioma-associated epilepsy are far to be completely understood. Using glioma-neurons co-cultures, we found that tumor cells are able to deeply influence neuronal chloride homeostasis, by depolarizing the reversal potential of γ-aminobutyric acid (GABA)-evoked currents (EGABA). EGABA depolarizing shift is due to zinc-dependent reduction of neuronal KCC2 activity and requires glutamate release from glioma cells. Consistently, intracellular zinc loading rapidly depolarizes EGABA in mouse hippocampal neurons, through the Src/Trk pathway and this effect is promptly reverted upon zinc chelation. This study provides a possible molecular mechanism linking glioma invasion to excitation/inhibition imbalance and epileptic seizures, through the zinc-mediated disruption of neuronal chloride homeostasis.

journal_name

Cell Death Dis

journal_title

Cell death & disease

authors

Di Angelantonio S,Murana E,Cocco S,Scala F,Bertollini C,Molinari MG,Lauro C,Bregestovski P,Limatola C,Ragozzino D

doi

10.1038/cddis.2014.437

subject

Has Abstract

pub_date

2014-10-30 00:00:00

pages

e1501

issn

2041-4889

pii

cddis2014437

journal_volume

5

pub_type

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