Transient microstructural brain anomalies and epileptiform discharges in mice defective for epilepsy and language-related NMDA receptor subunit gene Grin2a

Epilepsia
Manal SalmiPierre Szepetowski

Abstract

The epilepsy-aphasia spectrum (EAS) is a heterogeneous group of age-dependent childhood disorders characterized by sleep-activated discharges associated with infrequent seizures and language, cognitive, and behavioral deficits. Defects in the GRIN2A gene, encoding a subunit of glutamate-gated N-methyl-d-aspartate (NMDA) receptors, represent the most important cause of EAS identified so far. Neocortical or thalamic lesions were detected in a subset of severe EAS disorders, and more subtle anomalies were reported in patients with so-called "benign" phenotypes. However, whether brain structural alterations exist in the context of GRIN2A defects is unknown. Magnetic resonance diffusion tensor imaging (MR-DTI) was used to perform longitudinal analysis of the brain at 3 developmental timepoints in living mice genetically knocked out (KO) for Grin2a. In addition, electroencephalography (EEG) was recorded using multisite extracellular electrodes to characterize the neocortical activity in vivo. Microstructural alterations were detected in the neocortex, the corpus callosum, the hippocampus, and the thalamus of Grin2a KO mice. Most MR-DTI alterations were detected at a specific developmental stage when mice were aged 30 days, but not at...Continue Reading

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Citations

Mar 15, 2020·Neurochemical Research·Yisi ShanZhiwei Gao
Sep 4, 2020·Journal of Neurochemistry·Thomas J TurnerGabriele Lignani
Dec 7, 2019·F1000Research·Scott J MyersChian-Ming Low
Jun 25, 2020·Brain : a Journal of Neurology·Ariadna AmadorWayne N Frankel
Dec 20, 2020·Expert Review of Neurotherapeutics·Krzysztof Łukawski, Stanisław J Czuczwar
Nov 2, 2021·Frontiers in Molecular Neuroscience·Xiao-Rong LiuWei-Ping Liao

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