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.
S Di Angelantonio, E Murana, S Cocco, F Scala, C Bertollini, et al.. A role for intracellular zinc in glioma alteration of neuronal chloride equilibrium.. Cell Death and Disease , Nature Publishing Group, 2014, 5, pp.e1501. 〈10.1038/cddis.2014.437〉. 〈pasteur-01182336〉
