RT Journal Article
SR Electronic
T1 Epileptiform GluN2B–driven excitation in hippocampus as a therapeutic target against temporal lobe epilepsy
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2021.06.30.450508
DO 10.1101/2021.06.30.450508
A1 Adam Gorlewicz
A1 Barbara Pijet
A1 Krstina Orlova
A1 Leszek Kaczmarek
A1 Ewelina Knapska
YR 2021
UL http://biorxiv.org/content/early/2021/07/01/2021.06.30.450508.abstract
AB NMDAR is an ionotropic glutamate receptor critically involved in excitatory synaptic transmission. The receptor properties are strongly determined by its subunit composition. One of the NMDAR subunits is GluN2B, which displays restricted and spatially different from other subunits expression in the mature brain. GluN2B–containing NMDARs are present in the hippocampus – a structure playing a major role in temporal lobe epilepsy (TLE). However, the contribution of GluN2B to pathophysiology of TLE has not been fully explored. Here, we report the functional alterations of GluN2B–containing NMDAR receptors in the hippocampus in distinct mouse models of temporal lobe epilepsy. In particular, we show the impact of GluN2B on excitatory feedback in granule cells. Based on these results, we propose a mechanism–oriented effective antiepileptic strategy that selectively antagonizes GluN2B–containing NMDARs with ifenprodil, a well–known GluN2B antagonist. Collectively, our research identifies GluN2B as one of the pivotal factors in pathogenesis of temporal lobe epilepsy and associated recurrent seizures. Furthermore, our study indicates the prospective antiepileptic properties of ifenprodil in TLE.Competing Interest StatementThe authors have declared no competing interest.