Efavirenz restored NMDA receptor dysfunction and inhibited epileptic seizures in GluN2A/Grin2a mutant mice

• DOI: 10.3389/fnins.2023.1086462
• Publication Date: 2023-03-02T04:48:03Z
• Authors: Teng Zhao; Rui Zhong; Xinyue Zhang; Guangjian Li; Chunkui Zhou; Shaokuan Fang; Ying Ding; Weihong Lin
• Keywords: loss of function; seizure; epilepsy; efavirenz; Neurosciences. Biological psychiatry. Neuropsychiatry; NMDA receptor; GluN2A/GRIN2A-V685G mutation; RC321-571; Neuroscience; 3. Good health

N-methyl-D-aspartate receptor (NMDAR) is one of the main excitatory neurotransmitter glutamate in brain, which key determinant excitatory/inhibitory balance neural network. GluN2A/GRIN2A subunits NMDAR and plays an important role epilepsy. Approximately 78% patients with GluN2A/Grin2a mutations have epilepsy, underlying mechanism this association not well characterized.We constructed a mouse model hyperthermic seizure, conducted vitro vivo electrophysiological behavioral studies to clarify pathogenic characteristics GluN2A/GRIN2A-V685G mutation. In addition, drug efavirenz (EFV), used treat HIV infection, was administrated mutant animals assess whether it can restore loss function.Mutant mice showed no significant change mRNA or protein expressions compared wild type (WT) mice. Mice mutation exhibited shorter latency increased frequency seizure-like events, decreased peak current area postsynaptic current, event micro-inhibitory WT They also threshold, amplitude, input resistance, root number action potential. EFV administration reversed these changes. The loss-of-function (LoF) changed network, rendering animal more prone seizures.EFV indicated hold its potential treatment inherited