Kainic acid-induced seizures activate GSK-3β in the hippocampus of D2R-/- mice

Neuroreport
Prem P TripathiYuri Bozzi

Abstract

Dopamine D2 receptor (D2R) signalling is implicated in limbic seizure propagation and seizure-induced neurodegeneration. D2R-/- mice display increased susceptibility to kainic acid (KA) seizures and seizure-induced apoptosis of hippocampal neurons. Here we further investigated the molecular pathways of KA-induced apoptosis in the D2R-/- hippocampus. Immunoblotting experiments showed a marked induction of caspase 3 in the D2R-/- but not in the wild-type hippocampus, 24 h after the administration of KA. The activation of the Akt/glycogen synthase kinase-3beta (GSK-3beta) pathway that has been implicated in neuronal apoptosis was also studied at the same time. No difference in Akt phosphorylation in the hippocampus was detected between the two genotypes, whereas GSK-3beta phosphorylation was markedly downregulated in D2R-/- mice. Our results suggest that GSK-3beta activation participates, independently of Akt, in the KA-induced apoptosis in the D2R-/- hippocampus.

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Citations

Oct 10, 2014·Psychiatry and Clinical Neurosciences·Ichiro KusumiYoshito Takahashi
Mar 27, 2018·European Journal of Neurology : the Official Journal of the European Federation of Neurological Societies·J A AlcantaraK D Valente
Apr 8, 2020·Frontiers in Cellular Neuroscience·Danira Toral-RiosVictoria Campos-Peña
Dec 20, 2018·Brain Plasticity·María Llorens-Martín
Nov 29, 2016·Frontiers in Neuroscience·Dubravka Svob StracGiuseppe Di Giovanni
May 28, 2020·International Journal of Molecular Sciences·Runxuan LinPatrick Kwan
Oct 24, 2018·ACS Chemical Neuroscience·Najat AourzAlexander D Crawford

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Apoptosis

Apoptosis is a specific process that leads to programmed cell death through the activation of an evolutionary conserved intracellular pathway leading to pathognomic cellular changes distinct from cellular necrosis